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the study of anosognosia
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the study of anosognosia
Edited by
George P. Prigatano, Ph.D.
1
2010
1 Oxford University Press, Inc., publishes works that further Oxford University’s objective of excellence in research, scholarship, and education. Oxford New York Auckland Cape Town Dar es Salaam Hong Kong Karachi Kuala Lumpur Madrid Melbourne Mexico City Nairobi New Delhi Shanghai Taipei Toronto With offices in Argentina Austria Brazil Chile Czech Republic France Greece Guatemala Hungary Italy Japan Poland Portugal Singapore South Korea Switzerland Thailand Turkey Ukraine Vietnam
Copyright 2010 by Oxford University Press, Inc. Published by Oxford University Press, Inc. 198 Madison Avenue, New York, New York 10016 www.oup.com Oxford is a registered trademark of Oxford University Press, Inc. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission of Oxford University Press Library of Congress Cataloging-in-Publication Data The study of anosognosia / George P. Prigatano, editor. p. ; cm. Includes bibliographical references and index. ISBN-13: 978-0-19-537909-9 (alk. paper) ISBN-10: 0-19-537909-8 (alk. paper) 1. Anosognosia. 2. Nervous system—Degeneration—Rehabilitation. 3. Hemiplegia. I. Prigatano, George P. [DNLM: 1. Agnosia—psychology. 2. Agnosia—rehabilitation. 3. Awareness. 4. Hemiplegia. 5. Neurodegenerative Diseases—psychology. 6. Neurodegenerative Diseases—rehabilitation. WL 340 S9335 2009] RC553.C64S78 2009 616.80 0471—dc22 2009024065
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To Dagmar, Laura, and Katie
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Preface
The study of anosognosia is important for several reasons: 1. Patients with identifiable brain disorders (e.g., cerebrovascular accident [CVA], severe traumatic brain injury [TBI], etc.) may have reduced self-awareness of residual neurological or neuropsychological impairments that negatively impact their clinical care. 2. Understanding the biological and neuropsychological mechanisms responsible for anosognosia in its various forms may reveal important insights into brain organization and how human consciousness (subjective awareness of the self and the environment) is possible. 3. The comparative study of anosognosia in patients with identifiable brain disorders in comparison to patients with psychiatric disorders (e.g., hysterical, conversion disorder) may provide rich insights into the ‘‘body–mind’’ problem. 4. Understanding the basis of how anosognosia changes with time (i.e., ‘‘recovers’’ or ‘‘worsens’’) may provide important insights into mechanisms of ‘‘recovery’’ and ‘‘deterioration’’ after various brain disorders. This has clear implications for treatment and patient management.
It is, therefore, with considerable pleasure that this volume has become a reality. Hopefully, it will encourage clinicians and researchers to continue creative work in this area of investigation. This text is the direct result of a conference held in Phoenix, Arizona, at the Arizona Biltmore Hotel between October 24 and 27, 2008. Prominent clinicians and researchers who have studied anosognosia were willing to prepare chapters prior to meeting at the conference. During the conference they presented their ideas to the various participants. The authors then modified their chapters after the meeting concluded, to help clarify the new findings and review present and old theoretical perspectives. Additional chapters were added after the conference to cover topics not addressed at that time. The expressed goal of the conference and of this book was to summarize advances in the study of anosognosia. It is hopeful that readers and reviewers of this edited text will conclude that this has been achieved. The text does not cover all possible studies relevant to understanding anosognosia, but it does provide a summary of hundreds of studies that have bearing on this topic. I am indebted to the various authors who have taken seriously the need vii
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PREFACE
to summarize important findings relevant to the study of anosognosia. Chapter lengths within this volume vary, but they do so primarily because of the databases that presently exist. Clearly, there is more to say in some areas than in others. In the initial section of this book, chapters are devoted to the study of anosognosia for hemiplegia (AHP). These chapters repeat certain historical observations and models that have helped explain this phenomenon. This is necessary because each set of authors needed to set the stage for their particular approach to the study of AHP. Repetition can also be valuable insofar as it helps reveal how the same historical observations have impacted individual investigators differentially, thus modifying their focus of attention when conducting research. As is true in all of science, advances represent the unique interests of investigators and the body of research knowledge that they find most relevant. Other sections of this text have described how the study of anosognosia has expanded over the last several years. This expansion may, in part, have been stimulated by the first book that emanated from a similar conference on anosognosia that was held in Phoenix, Arizona, in October of 1988. That conference resulted in the edited text Awareness of Deficit after Brain Injury: Clinical and Theoretical Issues (Prigatano & Schacter, 1991). Both conferences were made possible by the generous support of the Barrow Neurological Institute at St. Joseph’s Hospital and Medical Center in Phoenix, Arizona. I have had the good fortune of being affiliated with the Barrow Neurological Institute (BNI) since 1985, and wish to express to hospital administrators, including Phil Pomeroy, Vice President of Neuroscience and Dr. Robert F. Spetzler, Director of the BNI, my gratitude for their continued support and encouragement. I would also like to explicitly recognize Dr. Spetzler for his continued efforts in providing support to carry out such an important meeting during difficult financial times. Funding from the Barrow Neurological Foundation (BNF) and the Newsome Foundation made this conference possible. Special recognition and thanks also goes to Lindsey Kerby, conference planning manager for the BNI, and to Mary Henry, administrative assistant in the Department of Clinical Neuropsychology. Ms. Henry’s work in preparing this manuscript is especially appreciated. Jennifer Gray, Ph.D., was invaluable in her help editing the chapters of this book. The continued goal of the Department of Clinical Neuropsychology within the Barrow Neurological Institute at St. Joseph’s Hospital and Medical Center is to provide patient care based on our most recent scientific understanding of how various brain disorders affect psychological functioning. This needs to be done, however, in a manner that is sensitive to each individual’s personal reaction to his or her neurological and neuropsychological disturbances. This book represents our most recent efforts in this regard. George P. Prigatano, Ph.D., Newsome Chair, Clinical Neuropsychology
Contents
Contributors
xiii
Part I Historical Overview and Introduction 1
1. Historical Observations Relevant to the Study of Anosognosia 3 George P. Prigatano
Part II Anosognosia of Motor and Language Impairments 15
2. Anosognosia for Hemiplegia and Models of Motor Control: Insights from Lesional Data 17 Gabriella Bottini, Eraldo Paulesu, Martina Gandola, Lorenzo Pia, Paola Invernizzi, and Anna Berti 3. Anosognosia for Hemiparesis and Hemiplegia: Disturbed Sense of Agency and Body Ownership 39 Hans-Otto Karnath and Bernhard Baier 4. The Insular Cortex and Subjective Awareness A. D. (Bud) Craig
63
5. Anosognosia and Anosodiaphoria of Weakness 89 Kenneth M. Heilman and Michal Harciarek ix
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CONTENTS
6. Anosognosia in Aphasia Andrew Kertesz
113
7. Assessing Anosognosia for Motor and Language Impairments 123 Gianna Cocchini and Sergio Della Sala Part III Anosognosia Observed in Various Brain Disorders 145
8. Anosognosia in Huntington’s Disease 147 Daniel Tranel, Jane S. Paulsen, and Karin F. Hoth 9. Anosognosia and Parkinson’s Disease 159 George P. Prigatano, Franziska Maier, and Richard S. Burns 10. Anosognosia in Alzheimer’s Disease: Neuroimaging Correlates 171 Sergio E. Starkstein and Brian D. Power 11. Anosognosia and Alzheimer’s Disease: Behavioral Studies 189 Alfred W. Kaszniak and Emily C. Edmonds 12. Anosognosia after Traumatic Brain Injury 229 George P. Prigatano 13. Anosognosia in Schizophrenia and Other Neuropsychiatric Disorders: Similarities and Differences 255 James Gilleen, Kathryn Greenwood, and Anthony S. David
CONTENTS
xi
Part IV Anosognosia and Specific Cognitive and Affective Disturbances 291
14. Anosognosia and Personality Change in Neurodegenerative Disease 293 Katherine P. Rankin 15. Anosognosia and Error Processing in Various Clinical Disorders 321 Ian H. Robertson 16. Emotional Awareness among Brain-Damaged Patients 333 Ricardo E. Jorge
Part V Anosognosia and Hysteria
357
17. Neuroanatomy of Impaired Body Awareness in Anosognosia and Hysteria: A Multicomponent Account 359 Roland Vocat and Patrik Vuilleumier
Part VI Measurement Issues and Technology 405
18. Functional Imaging of Self-Appraisal 407 Sterling C. Johnson and Michele L. Ries 19. The Behavioral Measurement of Anosognosia as a Multifaceted Phenomenon 429 M. Donata Orfei, Carlo Caltagirone, and Gianfranco Spalletta
Part VII Anosognosia and Visual Loss
453
20. Anton’s Syndrome and Unawareness of Partial or Complete Blindness 455 George P. Prigatano and Thomas R. Wolf
CONTENTS
xii Part VIII Advances in the Study of Anosognosia 469
21. A Progress Report on the Study of Anosognosia 471 George P. Prigatano 22. Management and Rehabilitation of Persons with Anosognosia and Impaired Self-Awareness 495 George P. Prigatano and Jeannine Morrone-Strupinsky
Author Index
517
Subject Index
525
Contributors
Bernhard Baier, M.D. Department of Neurology University of Mainz Mainz, Germany Anna Berti, M.D., Ph.D. Department of Psychology Neuropsychology Research Group University of Turin Turin, Italy Gabriella Bottini, M.D., Ph.D. Psychology Department University of Pavia Pavia, Italy Richard S. Burns, M.D. Barrow Neurological Institute St. Joseph’s Hospital and Medical Center Phoenix, Arizona Carlo Caltagirone, M.D. Department of Clinical and Behavioural Neurology IRCCS S. Lucia Foundation Rome, Italy Gianna Cocchini, Ph.D. Psychology Department Goldsmiths University of London London, England A. D. (Bud) Craig, Ph.D. Atkinson Research Lab Barrow Neurological Institute Phoenix, Arizona xiii
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CONTRIBUTORS
Anthony S. David, M.D. Department of Psychiatry Section of Cognitive Neuropsychiatry Institute of Psychiatry King’s College London, England Sergio Della Sala, M.D., Ph.D. Human Cognitive Neuroscience, Psychology University of Edinburgh Edinburgh, Scotland Emily C. Edmonds, M.A. Department of Psychology University of Arizona Tucson, Arizona Martina Gandola, M.A., Ph.D. Psychology Department University of Pavia Pavia, Italy James Gilleen, Ph.D. Department of Psychiatry Section of Cognitive Neuropsychiatry Institute of Psychiatry King’s College London, England Kathryn Greenwood, Ph.D. Department of Psychology Institute of Psychiatry King’s College London London, England Michal Harciarek, Ph.D. Institute of Psychology University of Gda nsk Gda nsk, Poland Kenneth M. Heilman, M.D. Department of Neurology College of Medicine University of Florida Veteran’s Affairs Medical Center Gainesville, Florida
CONTRIBUTORS
Karin F. Hoth, Ph.D. Division of Psychosocial Medicine Department of Medicine National Jewish Health Department of Psychiatry University of Colorado Denver Denver, Colorado Paola Invernizzi, M.A. Psychology Department Univeristy of Milano-Bicocca Milano, Italy Sterling C. Johnson, Ph.D. Geriatric Research Education and Clinical Center Wm. S. Middleton Memorial Veteran’s Hospital University of Wisconsin School of Medicine and Public Health Madison, Wisconsin Ricardo E. Jorge, M.D. Department of Psychiatry University of Iowa Hospitals and Clinics Iowa City, Iowa Hans-Otto Karnath, M.D., Ph.D. Section of Neuropsychology Center of Neurology Hertie-Institute for Clinical Brain Research University of T€ ubingen, T€ ubingen, Germany Alfred W. Kaszniak, Ph.D. Department of Psychology University of Arizona Tucson, Arizona Andrew Kertesz, M.D., FRCP (C) Department of Neurology University of Western Ontario St. Joseph’s Health Center London, Ontario, Canada Franziska Maier, M.A. Movement Disorders and Deep Brain Stimulation Department of Neurology University Hospital Cologne Cologne, Germany
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CONTRIBUTORS
Jeannine Morrone-Strupinsky, Ph.D. Department of Clinical Neuropsychology Barrow Neurological Institute St. Joseph’s Hospital and Medical Center Phoenix, Arizona M. Donata Orfei, M.A. Department of Clinical and Behavioural Neurology IRCCS S. Lucia Foundation Rome, Italy Eraldo Paulesu, M.D. Psychology Department Univeristy of Milano-Bicocca Milano, Italy Jane S. Paulsen, Ph.D. Departments of Psychiatry, Neurology, and Psychology College of Medicine University of Iowa Iowa City, Iowa Lorenzo Pia, Ph.D. Department of Psychology Neuropsychology Research Group University of Turin Turin, Italy Brian D. Power, M.D. Lecturer, School of Psychiatry and Neurosciences University of Western Australia Fremantle, Australia George P. Prigatano, Ph.D. Department of Clinical Neuropsychology Barrow Neurological Institute St. Joseph’s Hospital and Medical Center Phoenix, Arizona Katherine P. Rankin, Ph.D. Memory and Aging Center Department of Neurology University of California San Francisco San Francisco, California Michele L. Ries, Ph.D. Geriatric Research Education and Clinical Center
CONTRIBUTORS
Wm. S. Middleton Memorial Veteran’s Hospital University of Wisconsin School of Medicine and Public Health Madison, Wisconsin Ian H. Robertson, Ph.D., MRIA School of Psychology and Institute of Neuroscience Trinity College Dublin Dublin, Ireland Gianfranco Spalletta, M.D., Ph.D. Department of Clinical and Behavioural Neurology IRCCS S. Lucia Foundation Rome, Italy Sergio E. Starkstein, M.D., Ph.D. School of Psychiatry and Neurosciences University of Western Australia Fremantle, Australia Daniel Tranel, Ph.D. Departments of Neurology and Psychology Division of Behavioral Neurology and Cognitive Neuroscience College of Medicine University of Iowa Iowa City, Iowa Roland Vocat, Ph.D. Laboratory for Behavioral Neurology and Imaging of Cognition Department of Neuroscience University Medical Center & Department of Neurology University Hospital Geneva, Switzerland Patrik Vuilleumier, M.D. Laboratory for Behavioral Neurology and Imaging of Cognition Department of Neuroscience University Medical Center & Department of Neurology University Hospital Geneva, Switzerland Thomas R. Wolf, M.D. Consultant, Clinical Neuro-ophthalmology Instructor in Neurology and Visiting Research Scientist in Aerospace Medicine Mayo Clinic Arizona Phoenix, Arizona
xvii
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I
Historical Overview and Introduction
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1
Historical Observations Relevant to the Study of Anosognosia George P. Prigatano
The Nobel laureate Roger Sperry (1969) proposed that conscious awareness is ‘‘. . . a dynamic emergent property of cerebral excitation’’ (p. 533) that can have ‘‘. . . causal effects in brain function that control subset events in the flow pattern of neural excitation’’ (p. 533). He goes on to state that ‘‘. . . the conscious properties of cerebral patterns are directly dependent on the action of the component neural elements’’ (p. 534). With these comments, Sperry (1969) elevates conscious awareness to the highest of all integrative brain functions, and he notes that while it is dependent on underlying neural activity, it appears to emerge in such a fashion that it actually exerts some causal effect on other brain regions. If correct, this view suggests that the emergence of consciousness and ‘‘normal’’ self-awareness is an extremely important area of study for neuropsychology and the practice of all brain-related clinical disciplines. Disturbances in consciousness are indeed complex, and they may range from minor alterations to profound unawareness of one’s neurological and neuropsychological deficits. Persistent impairments in self-awareness appear to relate to a variety of cognitive and behavioral problems. They are also linked to poor decision making and may limit a person’s engagement in rehabilitation activities that potentially could be helpful to them. Efforts at neuropsychological rehabilitation of brain-dysfunctional patients several years ago emphasize this point (Prigatano et al., 1984). As a result, the study of anosognosia became a central topic for post-acute neuropsychological rehabilitation. It also became a central question for cognitive psychology, as it rediscovered the 3
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THE STUDY OF ANOSOGNOSIA
importance of ‘‘consciousness’’ in psychology (Prigatano & Schacter, 1991; Weiskrantz, 1997). This book attempts to summarize many of the contributions that have been made over the last 20 years that help advance our understanding of anosognosia. In order to put these advances into perspective, however, it is important that one have a reasonable grasp of both the remote and recent history of the study of anosognosia that impacts our present thinking about this phenomenon. Without such an historical perspective, it is difficult to separate out a ‘‘true’’ advance from an ‘‘apparent’’ advance. The latter is simply a restating of older observations using new terminology. While interesting, these ‘‘apparent’’ advances do not lead to a better, more useful explanation of the phenomenon. Equating the term ‘‘better’’ with ‘‘more useful’’ is intentional. If the terms used to explain the phenomenon are indeed ‘‘better,’’ they lead to more precise predictions and practical methods of intervention. This perspective will, therefore, guide a rather brief review of historical observations concerning the phenomenon of anosognosia that have relevance to the present volume.
Historical Accounts All historical accounts are shaded by the biases, and at times ignorance, of the historian. Consequently, multiple perspectives from different authors are often needed to get as close as one can to ‘‘what really happened in the past’’ to determine how it influences our present thinking (Prigatano, 2005). In their seminal book Denial of Illness: Symbolic and Physiologic Aspects, Edwin Weinstein and Robert Kahn (1955) provided the most comprehensive historical perspective on anosognosia, covering papers written from the late 1800s to the mid-1950s. MacDonald Critchley (1953) also discussed ‘‘unawareness of hemiparesis (anosognosia)’’ (p. 225) in his book The Parietal Lobes. His account is also interesting, as it provides an English translation of some of Babinski’s actual words when describing anosognosia for hemiplegia (see pp. 231–232). Critchley (1953) makes the important observation that ‘‘the patient’s attitude toward their inadequate motor performance forms an interesting problem . . .’’ (p. 233) that must also be understood in any scientific account of anosognosia (see Heilman & Harciarek, Chapter 5, this volume). Edoardo Bisiach and Giuliano Geminiani (1991) provide a brief, but valuable historical perspective beginning with observations from antiquity. Prigatano and Schacter (1991) further provide a historical review, which attempts to combine observations made by early neurophysiologists, psychiatrists, and neurologists. Further historical insights have subsequently been made (see Vocat & Vuilleumier,
HISTORICAL OBSERVATIONS
5
Chapter 17 and Kertesz, Chapter 6, this volume) that highlight Babinski’s observations concerning hysteria and Anton’s and Pick’s observations concerning anosognosia for hemiplegia. Since the early writings of Anton (1898), Pick (1898, 1908), and Babinski (1914), there have been a number of papers that have described various clinical observations and empirical findings concerning anosognosia. There have also been various models proposed to explain this complicated phenomenon. The goal of this book is to synthesize knowledge that has been accumulated over many years regarding the study of anosognosia and to specifically highlight advances that have occurred in the field.
What Constitutes an Advance? Table 1.1 lists the criteria for determining whether advances have occurred in the field. As it relates to the study of anosognosia and impaired self-awareness after brain injury, the first area to consider is whether there have been any new clinical observations that are relevant to the study of anosognosia that must be explained by any theory or model of anosognosia. The second type of advance to be considered is empirical findings, which use appropriate controlled observations that help enlighten our understanding of the underlying mechanism or mechanisms responsible for this phenomenon. The third area of advance to consider centers around whether new methods of study have emerged that allow the phenomenon to be more thoroughly studied. In this area, revolutionary advances have occurred, particularly over the last 10 years. Finally, we will consider whether there have been advances made in new, testable (and perhaps partially untestable) models/hypotheses that help guide the field to have a more comprehensive and detailed understanding of anosognosia and related disorders. Chapter 21 of this volume will summarize advances in the study of anosognosia. Before proceeding, however, it is worthwhile to stop and reflect on exactly what we mean by the term anosognosia.
Table 1.1 What Constitutes an Advance?
• New, relevant clinical observations that must be explained by any theory or model of anosognosia
• New empirical findings that clarify the nature of anosognosia and possible underlying mechanism(s) responsible for it
• New methods of study of the phenomenon of anosognosia • New testable (and perhaps partially untestable) models that are both more comprehensive and specific in their predictions about anosognosia and related disorders
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THE STUDY OF ANOSOGNOSIA
Definitions and Early Considerations If one were to consult the Internet (notably Wikipedia), the following definition of anosognosia is readily available to the public: ‘‘Anosognosia is a condition in which a person who suffers disability due to brain injury seems unaware of or denies the existence of his or her handicap. This may include unawareness of quite dramatic impairments such as blindness or paralysis. It was first named by neurologist Joseph Babinski in 1914, although relatively little has been discovered about the cause of the condition since its initial identification’’ (‘‘Anosognosia,’’ 2009, para. 1). As of March 10, 2009, a Google search of articles that include the term anosognosia produced 73,200 references. Of those references, 7,030 struggled with a clear definition of exactly what anosognosia means. Edoardo Bisiach and Giuliano Geminiani (1991) cautioned us about obtaining a truly scientific definition of anosognosia with their following observations: ‘‘A satisfactory definition of anosognosia per se is perhaps impossible, attributable to the fact that the term anosognosia, rather than referring to a truly distinct symptom, may be (and has indeed been) used to denote aspects of patients’ behavior in relationship to their illness that are heterogeneous in appearance and unlikely to depend on a specific set of causes exclusively related to them’’ (Bisiach & Geminiani, 1991, p. 19; emphasis added). According to Bisiach and Geminiani (1991), ‘‘Anosognosia deserves assessment tailored to each individual case, comprising faithful records of all relevant spontaneous behavior as well as of that instigated by the examiner’s queries, the limits to which are set only by the examiner’s inventiveness and the patient’s mood and intelligence’’ (p. 20). In light of these comments, a brief history regarding anosognosia will be presented as follows: observations made before Babinski; what Babinski observed and reported between 1914 and 1918; and observations after Babinski, which have led to the present report.
Anosognosia prior to Babinski Letters from antiquity provide descriptions of apparent denial or unawareness of profound sensory loss that appeared ‘‘incredible’’ to the observer (see Bisiach & Geminiani, 1991, p. 17). Persons who lose their vision may report the room as ‘‘dark,’’ but not self-recognize that they cannot see. Brian Kolb (1990), the noted neuroscientist and neuropsychologist, reported a similar phenomenon after his occipital stroke. He had to ‘‘discover’’ his loss of vision in one visual field. His initial impression that a light bulb had burned out when he attempted to turn on the kitchen light had to be replaced with the self-recognition that something had gone wrong with his own vision.
HISTORICAL OBSERVATIONS
7
In 1881 Hermann Munk conducted ablation studies on dogs and discovered a perplexing phenomenon (see Prigatano & Schacter, 1991). Lesions of the association cortex between primary visual and auditory centers produced a situation in which the dog appeared to be able to ‘‘see’’ (i.e., they would not bump into objects when moving), but they failed to recognize their master. He termed this phenomenon ‘‘mind blindness.’’ In a sense, it is an early animal model for agnosia and perhaps anosognosia. Recently on YouTube, there is a fascinating video clip of a dog that does not seem to recognize his own (left) hind leg. Could this be even a more striking example of anosognosia in nonprimates? The point of these observations is that for many years, before the formal study of neurology and neuropsychology, anosognosia or anosognostic phenomena were reported, and we continue to see various manifestations of these phenomena today. Babinski (1914) is credited for introducing the term anosognosia to the neurological community when he presented his findings to the French Neurological Society in June of 1914 and then again in December of 1918 (Bisiach & Geminiani, 1991). It has also been reported, however, that Gabriel Anton actually described anosognosia for hemiplegia prior to Babinski in 1893 (see Bisiach & Geminiani, 1991; Karnath & Baier, Chapter 3, this volume). Pick (1898) also reported apparent lack of awareness of left-sided motor deficits. Constantin von Monakow (1885) described apparent unawareness of cortical blindness, but his patients suffered from Korsakoff’s syndrome. It remained unclear whether the lack of awareness of visual loss was secondary to memory impairments, confabulatory tendencies, or a true ‘‘isolated’’ unawareness of visual impairments. Later, Anton (1898) reported cases of patients with visual loss that appeared clearly related to focal cerebral lesions (Weinstein & Friedland, 1977). The patients were not demented or confused. By providing a name for this phenomenon, Babinski (1914) introduced a whole new study within the field of neurology and later neuropsychology.
Babinski’s Observations and Use of the Term Anosognosia For non–French-speaking (and reading) investigators, the writings of Critchley (1953) are informative for understanding Babinski’s contributions. When describing ‘‘disorders of the body image,’’ Critchley (1953) noted that Babinski first employed the term anosognosia to refer to the lack of awareness of left hemiplegia. Critchley makes the following remarks concerning Babinski: As Babinski employed the word in 1914, however, the meaning was restricted so as to apply to cases of hemiplegia. In his original communication, Babinski drew attention to a mental disorder he had had the opportunity of observing in cerebral hemiplegia which consisted in the fact that the patients were unaware of, or seemed to be unaware of (ignorent ou paraissent ignorer), the existence of the paralysis
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THE STUDY OF ANOSOGNOSIA
with which they were afflicted. His first patient was a woman who had been paralysed down the left side for years, but who never mentioned the fact. If asked to move the affected limb she remained immobile and silent, behaving as though the question had been put to someone else. Babinski’s second patient was also a victim of left hemiplegia. Whenever she was asked what was the matter with her, she talked about her backache, or her phlebitis, but never once did she refer to her powerless left arm. When told to move that limb, she did nothing and said nothing, or else a mere, ‘‘Voil`a, c’est fait!’’ During a consultation, when her doctors were discussing the merits of physiotherapy in her presence, she broke in . . . ‘‘Why should I have electrical treatment? I am not paralysed.’’ In his second paper on the subject (1918), Babinski drew attention to two clinical points in his cases; both patients had sensory impairment down the affected side, and both had left-sided involvement. ‘‘Could it be,’’ wrote Babinski, ‘‘that anosognosia is peculiar to lesions of the right hemisphere?’’ This remark of Babinski’s in 1918 was a shrewd one, for clinical evidence since that date had shown that in the great majority of cases lack of awareness of hemiplegia amounts to a lack of awareness of a left hemiplegia. (p. 231)
Anosognosia after Babinski: Some Key Observations Critchley’s (1953) discussion of Babinski’s contribution is followed by a review of several authors’ perspectives regarding disorders of body image that were accumulated in the 1920s, 1930s, and 1940s. Critchley (1953) also cites an earlier paper by Weinstein and Kahn (1950), in which they report a patient believing that her left hand actually belonged to the nurse that was involved in her care (p. 236). Couched in the context of body disorders, Critchley felt it was important to separate unawareness of hemiparesis (anosognosia) from denial of hemiparesis in which confabulation was present. The presence of confabulatory tendencies was thought to reveal a psychotic state that rendered the patient’s judgment about many things unreliable and not necessarily reflective of an underlying specific neurological disorder of awareness. Weinstein and Kahn (1955) have championed this latter point of view. They considered denial a form of breakdown in reality testing that had nothing to do with a specific lesion producing a specific awareness deficit. They went on to argue that a lesion in the frontal lobes or parietal lobes will determine what type of deficit a patient may have, but not the mechanism of denial (Weinstein & Kahn, 1955, p. 123) (see Table 1.2). In speaking with Weinstein a few years before his death, he indicated that he wished that he could retract that statement (personal communication with Ed Weinstein, approximately 1995). The point, however, is that Weinstein and Kahn’s (1955) very influential book moved the field of the study of anosognosia out of neurology into psychiatry, and with it, there was a loss of interest in studying the neuropsychological basis of this phenomenon for many years.
HISTORICAL OBSERVATIONS
9
Table 1.2 Salient Observations Regarding Anosognosia after Babinski Nielsen (1938) Sandifer (1946) Weinstein & Kahn (1955)
Germann et al. (1964) Roeser & Daly (1974) Bisiach et al. (1986)
‘‘I must believe my feelings.’’ ‘‘That’s my ring on your hand, doctor.’’ ‘‘. . . various forms of anosognosia are not discrete entities that can be localized in different areas of the brain. Whether a lesion involves the frontal or parietal lobe determines the disability that may be denied, but not the mechanism of denial.’’ (p. 123) ‘‘The right side of the car took up too much space on the road.’’ ‘‘The right foot failed to come into bed.’’ ‘‘Something is wrong with the stereo.’’ Anosognosia of hemiplegia can be disassociated from anosognosia of hemianopsia in the same patient.
In addition to Babinski’s clinical reports, however, a number of other authors have made important clinical observations that need to be kept in mind when evaluating any potential ‘‘new observations.’’ Perhaps the first and most poignant observations that were made that are relevant to this volume were those by Nielsen (1938). Nielsen describes a patient who had paralysis of her left arm. When it was brought to her attention that this was, in fact, her arm, she stated that even though she was temporarily convinced that it was her arm, it did not ‘‘feel like her arm.’’ Therefore, she could not really accept that it was her arm (see Critchley, 1953, p. 236). This early observation by Nielsen emphasized the importance of feeling states in the phenomenon of anosognosia for hemiplegia. A few years later, Sandifer (1946) described in detail a case of a patient who was anosognostic for left hemiplegia. Sandifer recorded verbatim statements of what the doctor and patient said to one another, providing a classic description of the phenomenon. In addition to being unaware of the hemiparesis, the patient used a bizarre form of logic to explain apparent discrepancies in perception that may also be related to the phenomenon of anosognosia. At one point, the examining physician asked the patient: ‘‘Is this your hand?’’ The patient responded: ‘‘Not mine, doctor.’’ The physician responded: ‘‘Whose hand is it then?’’ The patient responded: ‘‘I suppose it’s yours, doctor.’’ Later, after several other questions, the physician again asked the patient: ‘‘Is this your hand?’’ Again, the patient responded: ‘‘Not mine, doctor.’’ The physician then says: ‘‘Yes it is. Look at the ring. Whose is it?’’ The patient then responded: ‘‘That’s my ring; you’ve got my ring, doctor.’’ Instead of recognizing the obvious differences in the hands, the patient focused on the fact that her ring appeared to be on the hand of the physician and not her own hand. These types of phenomena have led both researchers and clinicians to recognize that anosognosia is indeed a complicated phenomenon and has many overlapping symptoms. It seems to involve not only cognitive and perceptual disturbances, but perhaps disturbances in various ‘‘belief’’ systems. Bisiach and Geminiani (1991) also addressed this issue.
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Figure 1.1 Presenters/authors of the initial conference on anosognosia held in 1988 in Phoenix, AZ. Back row, from left to right: David Schacter, Alfred Kaszniak, Edwin Weinstein, John Kihlstrom, Edoardo Bisiach. Front row, from left to right: Kenneth Heilman, Lisa Lewis, George Prigatano, Susan McGlynn, Marcia Johnson, Donald Stuss.
There are, however, other accounts that often are not given adequate attention. One was written by William Germann (Germann, Flanigan, & Davey, 1964), who was a practicing neurosurgeon when he suffered a subdural hematoma secondary to a roller coaster ride at Disneyland in Los Angeles. Germann appeared to have a lack of awareness of right-sided neglect, as opposed to left-sided neglect. His description highlighted that one may have unawareness as a consequence of a left-sided brain injury, as opposed to purely right-sided brain injury. It also emphasized that in very capable individuals who are quite aware of anosognostic phenomena, there is a tendency not to recognize this deficit when it occurs in oneself. A case report by Roeser and Daly (1974) provides an example of a patient who had a thalamic lesion: the patient was arguing that something was wrong with her stereo, but she was not aware that there was something wrong with her own perception of music. Again, this phenomenon highlights that an impairment or loss of a sensorimotor function is not readily attributed to oneself, but often some form of external explanation is provided to explain an apparent failure. Finally, in modern times, several insightful observations about anosognosia were made by Edoardo Bisiach and his colleagues. Bisiach et al. (1986) were able to demonstrate for the first time that one could separate anosognosia for hemiplegia from anosognosia for hemianopsia in the very same patient. This was a
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strong argument for some type of modular representation of awareness of a given function. It also was an argument that conscious awareness may reflect the highest organization of that modular function. To further discuss modern perspectives of anosognosia, a conference was held in 1988 in Phoenix, Arizona. At the conference, prominent clinicians and researchers discussed varying views concerning the nature of impaired selfawareness in different brain disorders. These discussions led to the book Awareness of Deficit: Clinical and Theoretical Issues (Prigatano & Schacter, 1991). At that conference, Edoardo Bisiach, Edwin Weinstein, Kenneth Heilman, and others presented their ideas. Figure 1.1 includes a picture of some of the individual presenters/authors who were involved in the first Phoenix conference on anosognosia. As noted in the Preface, a second conference was held in Phoenix, Arizona, in 2008. Again, several leaders in the field of impaired self-awareness or anosognosia met to discuss recent research findings and theoretical perspectives. The chapters that follow highlight many of the ideas presented at that meeting. Figure 1.2 is a picture of the individual presenters (authors) that gathered in Phoenix for this second meeting.
Figure 1.2 Presenters/authors of the second conference on anosognosia held in 2008 in Phoenix, AZ. Back row from left to right: Sergio Starkstein, Ricardo Jorge, Claudia Cacciari, Sterling Johnson, Franziska Maier, Alfred Kaszniak, Hans-Otto Karnath, Ian Robertson, Gabriella Bottini, Patrik Vuilleumier. Middle row from left to right: Gianna Cocchini, Maria Donata Orfei, Katherine Rankin. Front row from left to right: Bud Craig, Andrew Kertesz, Kenneth Heilman, George Prigatano, Daniel Tranel, Anthony David.
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‘‘Blindsight:’’ Does It Have Anything to Tell Us about Anosognosia? In his profoundly thoughtful and scholarly book Consciousness Lost and Found, Larry Weiskrantz (1997) reminds us that there is a ‘‘flip side’’ to the problem of anosognosia. Instead of the patient not being aware of a loss in neurological or neuropsychological functioning, the patient may be unaware of preserved neurological/ neuropsychological functioning following significant brain pathology. The study of patients with profound visual loss who have retained some visual capacity for which they are unaware highlights this point. Understanding the neuroanatomical substrates of blindsight may help us understand the importance of certain anatomical regions that underlie the phenomenon of anosognosia for complete blindness. Weiskrantz (1997) struggled with the broader problem of what consciousness is and humbly admitted that ‘‘the solution to the thorny problem of conscious awareness and its neurological basis’’ (p. 4) has not been solved by any of us. His observation remains true to this day. As this volume will demonstrate, we have, in fact, made some advances in the scientific study of anosognosia, but we still have a considerable distance to go before we understand the phenomenon. In preparation for reading the chapters that follow, it is important to keep in mind that there are certain questions that, if answered, may in fact advance our knowledge of this important phenomenon.
Questions That Need to Be Answered in Order to Advance the Study of Anosognosia Advances in science are often unexpected, but detected by the ‘‘experienced mind’’ or the ‘‘prepared observer.’’ One cannot say where or when a true advance is most likely to occur. However, keeping in mind certain questions may prepare us to detect important advances. Below are a series of questions worth thinking about when reading the various chapters that follow. At the end of this book, I will refer back to these questions in an effort to consolidate how we presently view the phenomenon of anosognosia and to specifically address the question of whether advances have occurred in our understanding of this phenomenon over the last 20 years. 1. Are we any closer today to a scientific definition of anosognosia for hemiplegia than Babinski was in 1914? 2. What have recent studies revealed regarding the mechanism or mechanisms responsible for anosognosia for hemiplegia? 3. Why does anosognosia for hemiplegia seem to change rapidly for some patients and not for others? 4. Why is anosognosia for hemiplegia frequently associated with anosodiaphoria? 5. Why is anosognosia for hemiplegia at times associated with somatoparaphrenia?
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6. What role, if any, does the patient’s premorbid personality play in anosognosia for hemiplegia? 7. Why is anosognosia for hemiplegia most commonly observed following large lesions of the brain secondary to stroke, rather than small focal lesions? 8. Is anosognosia for hemiplegia commonly associated with both cortical and subcortical lesions? If so, why? 9. What advances have been made in understanding Anton’s syndrome? 10. What have recent studies revealed regarding the mechanism or mechanisms responsible for anosognosia for aphasia? 11. Is there any new information regarding the mechanism or mechanisms of unawareness of auditory perceptual skills, as described by Roeser and Daly (1974), after thalamic lesions? 12. What are the neurological/neuroanatomical, neurophysiological, and neuropsychological changes associated with hysterical sensorimotor loss? Are they different from what is observed in anosognosia for hemiplegia? 13. Do milder forms of anosognosia exist for cognitive, motor, perceptual, emotional, and motivational functioning in different patient groups? 14. Why do some brain-dysfunctional patients show anosognosia or impaired selfawareness, and patients with other disorders do not? 15. Are there neurotransmitter disturbances specifically associated with anosognosia? 16. Is anosognosia a purely cognitive, perceptual dysfunction? What role do emotions or feelings play in anosognostic conditions? 17. How is it possible that a patient can return to consciousness, be oriented to time and place, and remember what is being said, and still be unaware of a neurological or neuropsychological impairment? 18. Why is it that we cannot predict which patients will show anosognosia by just looking at their MRI scans of the brain or reviewing their medical history? 19. Why is anosognosia seldom reported in children? 20. What are the neuroimaging correlates of normal self-awareness in individuals with no neurologic conditions? Do they change in the presence of anosognosia? 21. Do disturbances in self-awareness observed in psychiatric patients have a neurological basis (i.e., a direct effect of brain dysfunction)? Do they represent some type of functional disturbance due to the emotional state of the patient? How does one separate out impaired self-awareness due to a neurological problem versus denial of disability? 22. Can anosognosia or impaired self-awareness coexist with denial of illness? 23. What measurement issues need to be kept in mind when studying anosognosia? 24. Is there any effective way of treating or at least managing anosognosia or impaired self-awareness (ISA) after brain disorder?
References Anosognosia (2009, March 4). In Wikipedia, the free encyclopedia. Retrieved March 10, 2009, from http://en.wikipedia.org/wiki/Anosognosia
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Anton, G. (1898). Ueber Herderkrankungen des Gehirnes, welche von Patienten selbst nicht wahrgenommen warden. Wiener Klinische Wochenschrift, 11, 227–229. Babinski, J. (1914). Contribution a` l’etude des troubles mentaux dans l’hemiplegie organique cerebrale (Anosognosie). Revue Neurologique, 27, 845–847. Bisiach, E., & Geminiani, G. (1991). Anosognosia related to hemiplegia and hemianopia. In G. P. Prigatano & R. L. Schacter (Eds.), Awareness of deficit after brain injury: Clinical and theoretical issues (pp. 17–39). New York: Oxford University Press. Bisiach, E., Vallar, G., Perani, D., Papagno, C., & Berti, A. (1986). Unawareness of disease following lesions of the right hemisphere: Anosognosia for hemiplegia and anosognosia for hemianopia. Neuropsychologia, 24(4), 471–481. Critchley, M. (1953). The parietal lobes. New York: Hafner Press. Germann, W. J., Flanigan, S., & Davey, L. M. (1964). Remarks on subdural hematoma and aphasia. Clinical Neurosurgery, 12, 344–350. Kolb, B. (1990). Recovery from occipital stroke: A self-report and an inquiry into visual processes. Canadian Journal of Psychology, 44, 130–147. Nielsen, J. M. (1938). Disturbances of the body scheme: Their physiological mechanism. Bulletin of the Los Angeles Neurology Society, 3, 127–135. Pick, A. (1898). Beitr€age zur Pathologie und pathologischen Anatomie des Centralnervensystems. Berlin: Karger. Pick, A. (1908). Ueber St€orungen der Orientierung am eigenen K€orper. Arbeiten aus der psychiatrischen. In Universtats-klinic in Prag (pp. 1–19). Berlin: Karger. Prigatano, G. P. (2005). A history of cognitive rehabilitation. In P. Halligan & D. Wade (Eds.), The effectiveness of rehabilitation for cognitive deficits (pp. 3–10). New York: Oxford University Press. Prigatano, G. P., Fordyce, D. J., Zeiner, H. K., Roueche, J. R., Pepping, M., & Wood, B. (1984). Neuropsychological rehabilitation after closed head injury in young adults. Journal of Neurology, Neurosurgery and Psychiatry, 47, 505–513. Prigatano, G. P., & Schacter, D. L. (1991). Awareness of deficit after brain injury: Clinical and theoretical issues. New York: Oxford University Press. Roeser, R. J., & Daly, D. D. (1974). Auditory cortex disconnection associated with thalamic tumor: A case report. Neurology, 24, 555–559. Sandifer, P. H. (1946). Anosognosia and disorders of body scheme. Brain, 69, 122–137. Sperry, R. W. (1969). A modified concept of consciousness. Psychological Review, 76(6), 532–536. von Monakow, C. (1885). Experimentelle und pathologisch-anatomische Untersuchungen u €ber die Beziehungen der sogentannen Sehsph€are zu den infracorticalen Opticuscentren und zum N. opticus. Archiv F€ ur Psychiatri, und Nervenkrankheiten, 16, 151–199. Weinstein, E. A., & Friedland, R. P. (Eds.) (1977). Hemi-inattention and hemisphere specialization. New York: Raven Press. Weinstein, E. A., & Kahn, R. L. (1950). The syndrome of anosognosia. Archives of Neurology and Psychiatry, 64, 772–791. Weinstein, E. A., & Kahn, R. L. (1955). Denial of illness: Symbolic and physiological aspects. Springfield, IL: Charles C. Thomas. Weiskrantz, L. (1997). Consciousness Lost and Found: Neuropsychological exploration. New York: Oxford University Press.
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Anosognosia of Motor and Language Impairments
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Anosognosia for Hemiplegia and Models of Motor Control: Insights from Lesional Data Gabriella Bottini, Eraldo Paulesu, Martina Gandola, Lorenzo Pia, Paola Invernizzi, and Anna Berti
Anosognosia is a term generally used to denote a complete or partial lack of awareness of different neurological (e.g., hemianopia, hemiplegia, cortical blindness, cortical deafness) and/or cognitive dysfunctions, such as, for example, fluent aphasia or memory deficits (see Prigatano & Schacter, 1991, for a review). In 1914, Babinski first introduced the term anosognosia, describing in particular the denial of motor deficits contralateral to a brain lesion (Babinski, 1914). Clinically, this disturbance ranges from emotional indifference or anosodiaphoria (Babinski, 1914), in which patients admit the paralysis and simply minimize its severity, to a complete unawareness of the unilateral motor impairment. The classical assessment of anosognosia proposed by Bisiach, Vallar, Perani, Papagno, and Berti (1986), using a 0 to 3 point scale, allows us to discriminate between patients who simply deny the deficit (score: 2/3) but are still able to discover the impairment when an explicit action is requested, from patients who still remain anosognosic despite the obvious inability to perform a specific movement (for example, clapping one’s hand) requested by the examiner (score: 3/3). In this last case patients not only deny the impairment but present a false productive belief of having moved in spite of the evidence that a movement did not actually occur (‘‘active’’ delusional component of anosognosia). Delusional beliefs concerning the affected limb, such as somatoparaphrenia (Gerstmann, 1942), in which the ownership of the limb is ascribed to another person (e.g., doctor/examiner or a relative), misoplegia (e.g., hatred toward the affected limbs; Critchley, 1974), or personification (e.g., the hemiplegic limb is considered as an entity with an own identity), are usually considered as additional abnormal manifestations linked to anosognosia (referred to as ‘‘anosognosic phenomena’’; Cutting, 1978). Adopting a more general classification, 17
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all these symptoms may be distinguished as defective (anosognosia) or productive (somatoparaphrenia). Due to this dichotomy it has become difficult to consider all these productive manifestations as equally linked to anosognosia, as recently emphasized by Marcel, Tegner, and Nimmo-Smith (2004). This difficulty also derives from the historical definition of anosognosia as a negative/defective manifestation; thus, it becomes quite incoherent to consider the somatoparaphrenic delusion as a consequence of anosognosia. These two symptoms are typically strictly associated. Furthermore, anosognosia is frequently associated with unilateral neglect (Appelros, Karlsson, & Hennerdal, 2007; Bisiach et al., 1986; Rode et al., 1992; Rode, Perenin, Honore, & Boisson, 1998; Starkstein, Fedoroff, Price, Leiguarda, & Robinson, 1992; Willanger, Danielsen, & Ankerhus, 1981). The coexistence of these disturbances may be due to lesion of adjacent cerebral areas involving spatial processing and body representation. However, the observation of multiple dissociations between neglect, anosognosia, and delusional impairments of body schema suggests that neglect itself does not seem the crucial factor to elicit anosognosia and is not always present when anosognosia occurs (Berti, Ladavas, & Della Corte, 1996; Bisiach et al., 1986; Dauriac-Le Masson et al., 2002). The clinical manifestations of anosognosia for hemiplegia are of great interest because they may provide indirect information on the cognitive organization of motor control. In this chapter some of the cognitive models on motor control will be considered in order to understand the pathological mechanisms underlying anosognosia for hemiplegia. Furthermore, the anatomical substrates of this symptom will also be taken into account as a contribution to the comprehension of anosognosia for hemiplegia as an impairment of motor control. Finally, recent evidence concerning the intention to move and its role in anosognosia will be discussed.
Interpretations of Anosognosia The study of patients with anosognosia is of great interest for the comprehension of the neural mechanisms of body representation and motor awareness (review in Bisiach, 1995; Heilman, Barrett, & Adair, 1998; Vallar, Bottini, & Sterzi, 2003). Classically, the interpretations of anosognosia may be categorized into motivational and cognitive theories.
Motivational Theories of Anosognosia Motivational theories, such as Weinstein and Kahn’s (1955) psychodynamic interpretation of unawareness of the deficit, considered anosognosia as a psychological defensive mechanism or reaction aimed to protect the self from the potential distress deriving from suffering from a severe impairment or disease
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(Schilder, 1935; Weinstein & Kahn, 1955). On the other hand, cognitive theories interpreted the symptom as a consequence of a specific disorder due to the damage of specific brain regions. The motivational theories, although fascinating, have been abandoned due to mounting evidence that anosognosia is frequently associated with right hemispheric lesions and present during the acute phase of the disease (Berti et al., 1996; Bisiach & Geminiani, 1991). Furthermore, this disturbance may be selective (e.g., a patient may be unaware of his hemiplegia but completely aware of his hemianopia or aphasia; Berti et al., 1996) and could be transiently modulated by different physiological manipulations (Cappa, Sterzi, Vallar, & Bisiach, 1987; Geminiani & Bottini, 1992; Vallar, Sterzi, Bottini, Cappa, & Rusconi, 1990). Collectively, these data suggest that a psychological defensive mechanism explanation of anosognosia is improbable.
Levine’s ‘‘Discovery Theory’’ The fact that anosognosia implies a cognitive impairment has been emphasized by Levine and colleagues’ (1991) ‘‘discovery’’ theory. These authors suggest that the loss of a function would not be sufficient to produce by itself an immediate experience of loss; instead, the deficit would need to be discovered or inferred (Levine, Calvanio, & Rinn, 1991), and the lack of proprioceptive information together with additional cognitive defects would not enable the patients to ‘‘make the necessary observations and inferences to diagnose the paralysis’’ (Levine et al., 1991). However, since the first observation of Babinski (1914, 1918) it was emphasized that anosognosia did not seem to be related to global mental confusion or other intellectual deficits and more in general, somatosensory deficit, personal neglect, mental confusion, and global cognitive impairment do not necessarily co-occur with anosognosia (Berti et al., 1996; Bisiach et al., 1986; Marcel et al., 2004; Small & Ellis, 1996; Starkstein et al., 1992; Willanger et al., 1981). Cognitive disturbances cannot be therefore considered a prerequisite for anosognosia to emerge and persist (Bisiach & Geminiani, 1991; McGlynn & Schacter, 1989; Vuilleumier, 2004).
The Disconnection Hypothesis In 1965, Geschwind (1965a, 1965b) proposed a more neurologically based theory of the anosognosic behavior, suggesting the presence of an interhemispheric disconnection that would isolate speech areas from the sensory and proprioceptive information deriving from the right brain side (Geschwind, 1965a, 1965b). Deprived from any veridical sensory information from the right hemisphere, the left speech areas would produce a verbal confabulation when the patient was questioned about his hemiplegia. This theory attempts to explain the prevalence of anosognosia after right brain damage. However, as
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noted by Bisiach et al. (1986), patients who verbally deny their deficit should still be able to express it in a nonverbal modality, and no dissociations between verbal and nonverbal response modalities have ever been reported (Berti, Ladavas, Stracciari, Giannarelli, & Ossola, 1998). Moreover, a simple manipulation like placing the left paretic arm into the unaffected right visual field, providing additional and correct sensory feedbacks to the left hemisphere, seems to improve the awareness of the motor deficit only in a few number of patients, for example, in 5 out of 15 patients in the study of Adair et al. (1997).
Anosognosia as a Consequence of a Central Monitoring Mechanism Deficit Other models are based on the concept that anosognosia derives from a more pervasive awareness impairment, thus to be ascribed to damage of a central monitoring mechanism (Goldberg & Barr, 1991). Similarly, the conscious awareness system (CAS; McGlynn & Schacter, 1989) model explains selective forms of anosognosia with a disconnection of CAS from specific peripheral input modules damaged by the brain lesion.
Anosognosia as a Modality-Specific Monitoring System Impairment Further studies on the clinical manifestations of anosognosia suggest that this disorder represents the consequence of damage to a modality-specific monitoring system (e.g., a motor monitoring system for anosognosia for hemiplegia) rather than of a central executive system (Bisiach, 1995; Bisiach, Meregalli, & Berti, 1990). This may better explain selective and modality-specific forms of unawareness of neurological deficits and also the presence of ‘‘productive’’ symptoms such as somatoparaphrenia (Bisiach, 1995; Bisiach et al., 1990). This theory inspired the topological representation of egocentric space (TRES) model (Bisiach, 1995; Bisiach & Berti, 1987; Bisiach & Geminiani, 1991; Bisiach et al., 1990), which explains both negative and productive deficits of contralesional space-body representation as a consequence of a more general representational deficit called dyschiria (Bisiach & Berti, 1987; Zingerle, 1913). Layer I of TRES is the terminal of a sensory transducer that carries information about an external object or body parts; layer II is a sensory-driven (veridical) representational network that analyzes and synthesises contents of layer I; layer III is composed of autochthonous (nonveridical), internally driven topologically organized cell assemblies. In normal waking conditions, the activity of layer III is inhibited by layer II cell assemblies so that the nonveridical product of layer III does not arrive to layer IV or is considered as imaginary. Layer IV represents the veridical final output of body-space representation. Inactivation of different components of this model may lead to different deficits: a partial or complete
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inactivation of one side of layers II and III produces lack of representation in layer IV of half the side of the space causing defective phenomena such as unilateral neglect or anosognosia. On the other hand, when there is damage to one side of only layer II, layer III is free from the inhibitory activity of layer II cell assemblies, so that autochthonous and nonveridical representations reach layer IV and give rise to delusional contents such as somatoparaphrenia (for a review of the model, see Bisiach & Berti, 1995; Bisiach & Geminiani, 1991; Bisiach & Vallar, 2000).
Anosognosia as an Impairment of the ‘‘Intention to Move’’: The Feed-Forward Hypothesis More recent interpretations have searched for the pathogenetic mechanism of anosognosia in the context of models of motor control (Wolpert & Ghahramani, 2000; Wolpert, Ghahramani, & Jordan, 1995). Heilman (1991) proposed a feed-forward theory, which explains anosognosia as a deficit of the intentional system to formulate expectations of movement. This model implies that the intentional system activates at the same time as the motor system to perform the movement and a body representation as it should be after the movement execution. This representation is constantly compared with the afferent information. Heilman (1991) argues that if no expectations of movement are generated, then no failure of the movement itself can be detected. In hemiplegic patients, aware of their motor impairment, the monitor-comparator—or body representation—detects the mismatch between expectations of movement and the failed performance. Conversely, anosognosic patients do not ‘‘intend to move or prepare to move’’ (Heilman et al., 1998) their paretic limb (motor neglect), so that the comparator does not detect any mismatch. The authors proposed that this intentional network is centered on the dorsolateral (Brodmann’s areas 6 and 8) and the medial frontal lobe (supplementary motor area and cingulate gyrus), the inferior parietal lobe, the thalamus, and the basal ganglia (Heilman et al., 1998). This interpretation of anosognosia is supported by several studies (Adair et al., 1997; Gold, Adair, Jacobs, & Heilman, 1994). Furthermore, the interpretation of anosognosia as a manifestation of motor neglect is supported by the observation that caloric vestibular and optokinetic stimulations induce the transient remission of both hemiplegia and anosognosia (Vallar et al., 2003; Vallar, Guariglia, Nico, & Pizzamiglio, 1997). This fact suggests that anosognosia, at least in those patients with motor deficit not due to a primary defect, could be unawareness of a ‘‘higher-order neglect related disorder’’, namely the defective intention to execute the movement (Vallar et al., 2003). Although the Heilman model (1991) is extremely convincing, it is not completely clear how anosognosic patients who assert to have performed a movement, for example, clapping their hands, could have lost their intention to move as the unimpaired limb does move.
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The Feedback Hypothesis of Anosognosia Frith, Blakemore, and Wolpert (2000) emphasized that the Heilman (1991; Heilman et al., 1998) model does not completely explain the delusional component of anosognosia, whereby patients affirm to have performed a movement, in spite of evidence that a movement did not actually occur. In response, they proposed an alternative interpretation of anosognosia based on a complex model of motor control (Wolpert & Ghahramani, 2000; Wolpert et al., 1995). This model provides three levels of motor representation: actual, desired, and predicted states. Controllers and predictors are also included in this system: the former provide the motor commands, and the latter provide an internal representation of the future movement. Comparisons between the three levels may signal errors that are adjusted by the means of predictors and controllers. Errors originating by a difference between desired and actual states activate the controllers in order to modify the motor commands. On the other hand, errors generated by discrepancies between predicted and actual states improve the predictors functioning. Finally, errors produced by the comparison between the desired and the predicted states activate the controllers at the level of the mental practice in the absence of real movement. The authors proposed that in anosognosic patients the comparison between desired (i.e., instantaneous goal of the system) and predicted state (i.e., future state of the system) is preserved. The normal functioning of both—controllers, which issued the appropriate motor commands to achieve the desired state, and predictors, which estimated the sensory consequences of the action—induces the normal experience of initiating a movement. On the other hand, denial of the motor deficit would be caused by a failure to register the incongruence between predicted and actual sensory consequences of the action and a failure to use these discrepancies to update the operations of the predictors. This is because information derived from the sensory feedback about the actual state of the system is not available or neglected, due to a lesion in the parietal lobe (Frith et al., 2000). Clearly, the Heilman theory makes the neurophysiological prediction of a global damage of the system involved in motor planning; on the other hand, the Frith model is consistent with a distributed anatomical system for motor control, with a possible sparing of some specific components.
Anatomy of Anosognosia Anatomical investigations have the potential to provide information that can be used to test current models of anosognosia. Early studies have associated anosognosia with parietal lobe lesions that classically have been related to spatial unilateral neglect (Critchley, 1953; Gerstmann, 1942; Pia, Neppi-Modona, Ricci, & Berti, 2004). With regard to the problem of the anatomical correlates
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of anosognosia for hemiplegia, the main outstanding questions relate to the hemispheric lateralization of the lesion and the crucial brain regions, which when damaged induce the symptom (Pia et al., 2004). Regarding the first issue, several studies based on clinical observation (Bisiach et al., 1986), Wada test experiments (Adair, Gilmore, Fennell, Gold, & Heilman, 1995; Breier et al., 1995; Carpenter et al., 1995; Gilmore, Heilman, Schmidt, Fennell, & Quisling, 1992), and a recent meta-analysis (Pia et al., 2004) consider the right hemisphere pivotal for the pathogenesis of anosognosia. However, the role played by damage to the left hemisphere should be taken into account, because of the presence of linguistic deficits that might prevent proper investigation of anosognosia (Pia et al., 2004). Even more controversial is the issue of the crucial intrahemispheric site of lesion correlated to the genesis of this symptom. Several cortical and subcortical structures have been indicated as having a role in causing unawareness of motor deficits. Historically, right parietal or thalamic damage, including thalamo-parietal connections, has been considered a necessary prerequisite for the presence of anosognosia (Barkman, 1925; Potzl, 1925). The involvement of such areas and other subcortical regions such as the corona radiata, the internal capsule, and the basal ganglia has been confirmed by several studies (Bisiach et al., 1986; Ellis & Small, 1997; Small & Ellis, 1996). A recent metaanalysis of the major studies about the anatomical correlates of anosognosia published between 1983 and 2001 (Pia et al., 2004) concluded that the associated damage of the fronto-parietal or fronto-temporo-parietal cortices is the most frequent combination of lesions linked to the presence of anosognosia. Pia and colleagues (2004) found large involvement of subcortical structures (in particular of the basal ganglia) in 41% of the patients. Therefore, even if anosognosia has often been considered a deficit tightly linked to a parietal lesion, a review of the results of the past studies does not show a clear and sure prevalence of the role of damage in this structure in generating the anosognosic behavior. Nevertheless, these seminal studies leave several uncertainties. First of all, many of them are single cases. Second, although many of these reports contain very interesting descriptions of patients’ behavior, in general there is not clear information about the degree of anosognosia. Third, the severity of the neurological deficit that is denied is usually not detailed, and there is no mention of a standardized neurological exam. And finally, the anatomical conclusions are not based on a systematic exploration including a control group of hemiplegic patients with neglect and without anosognosia. Recent studies have adopted a more methodologically rigorous approach by enrolling specific control groups (Berti et al., 2005; Karnath, Baier, & Nagele, 2005). The goal is to identify the precise anatomical lesional pattern of anosognosia while considering the complexity of the motor system and motor awareness, as well as the variety of behavioral manifestations.
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Anosognosia out of the Parietal Cortex In a recent paper, Berti et al. (2005) explored the lesional pattern of anosognosia following strict methodological rules for the behavioral profile and anatomical mapping. The authors compared, using a voxel-based statistical analysis, the brain lesion distribution of 12 patients with anosognosia and 17 patients without anosognosia (all with right brain damage). Interestingly, they only enrolled subjects presenting with a complete left hemiplegia that had been investigated by a standardized neurological clinical examination (hemiplegia ¼ complete absence of movement). One patient (case RMA) presented with anosognosia without neglect. All the studied subjects were in the acute clinical phase. The anatomical lesional mapping was performed in the stereotactic space of Talairach and Tournoux (1988) using a standard MRI volume that conformed to that space as redefined by the Montreal Neurological Institute (MNI) space. Image manipulations were performed with the applications Analyze and MRIcro (Rorden & Brett, 2000). The lesion distribution was identified using a probabilistic Brodmann’s areas map released with MRIcro. The statistical significance of the occurrence of a brain lesion in a given group was based on two omnibus tests (chi-square test with Yates’ correction, and Mann-Whitney U test) and a voxel-by-voxel test, implemented in Matlab 6.5. The authors found a significant association of unawareness for motor deficit with lesion of the dorsal premotor cortex (Brodmann’s area 6), area 44, and the somatosensory and primary motor cortex. Brodmann’s area 46 and the insula were also involved (see Figure 2.1). It is interesting to note that the same lesional pattern (Brodmann’s area 6, 4, 44, and 3 and in the insula) was also found in patient RMA, who was anosognosic in the absence of neglect, attesting to the specificity of this anatomical correlate with the symptom of motor deficit denial. Conversely, in hemiplegic patients without anosognosia the premotor cerebral cortex was spared while a significant involvement of the subcortical white matter in the depth of the centrum semiovale was found. The fact that the brain damage of motor regions was not complete, as the supplementary motor cortex (SMA) and the pre-SMA were spared (see Figure 2.1; Berti et al., 2005), suggests that a representation of the conscious intention of action could still be available in anosognosic patients (Berti, Spinazzola, Pia, & Rabuffetti, 2007), supporting Frith’s interpretation of anosognosia. Karnath et al. (2005) compared the lesion distribution of 14 anosognosic patients in the acute phase of the disease with 13 patients aware of their motor deficit considered as the control group with a comparable frequency and severity of additional neurological defects, such as spatial neglect, hemianesthesia, and hemianopia. The subtractive anatomical comparison revealed a significant involvement of the posterior insular cortex. This region was less damaged in patients with hemiplegia/hemiparesis without anosognosia. The authors
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Figure 2.1 Brain areas with lesions associated with anosognosia (From Berti et al., 2005, reprinted with permission from the Association for the Advancement of Science, Science, 309(5733), 488–491.) (See Color Plate 2.1)
proposed that the posterior insula, which integrates different sensory inputs (e.g., sensory, motor, auditory, and vestibular; Mesulam & Mufson, 1985) has an important role in the construction of self-awareness. In our opinion, the main difference between the study conducted by Berti et al. (2005) and this one is that Karnath et al. (2005) enrolled patients with variable severity degree of the contralesional motor deficit ranging from hemiparesis to the complete absence of movement. Although the exploration of unawareness for mild motor impairments may certainly contribute to understanding the organization of motor control, we think that it is important to study anosognosic patients comparable for the degree of motor deficit, as it is not still clear whether there is only one kind of denial of the impairment. In patients showing a residual motor function, the firm belief of having performed a movement could still be ascribed to the left, although defective, motor activity in the contralesional arm.
The Role of the Intention to Move in Anosognosia As we have just commented, anosognosia can be interpreted in the context of the models of motor control and related to the impairment of some of the processes involved in motor monitoring and execution. Thus, anosognosia may depend on
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the lack of the intention to move, of the capacity to provide correct motor planning, or to compare different representations of the status of the motor system. Although many studies investigated motor functions in normal subjects, at different levels while performing tasks of explicit motor action, of motor imagery or motor awareness (Ehrsson, Spence, & Passingham, 2004; Jeannerod, 1994; Jeannerod & Decety, 1995; Lau, Rogers, Haggard, & Passingham, 2004; Stephan & Frackowiak, 1996), a systematic study integrating data derived from the investigation of normal subjects and evidence from the exploration of anosognosic patients is still lacking. A crucial issue for the comprehension of motor deficit denial is about the intactness of the intention to act. The anatomical correlates of motor intention components have been extensively investigated in normal subjects. In a seminal paper published in 1983 (Libet, Gleason, Wright, & Pearl, 1983), healthy subjects were asked to signal the exact moment when they reported the experience of ‘‘wanting’’ to perform a movement (intention/urge/decision to move; ‘‘W judgement’’) and when they become aware to initiate a movement (‘‘M judgement’’). These two subjective time judgments were correlated with both the precise onset of the real movement, measured by the EMG, and the readiness potential (RP), recorded by the EEG. The authors found that both W and M judgements preceded the onset of the actual movement (EMG onset), respectively, by about 200 and by 50–80 ms. Even more interesting was the result that the negative readiness potential precedes by several hundred milliseconds the W judgement. Libet and colleagues (1983) concluded that the neural process (RP potential) preceding a voluntary, self-generated action starts before the appearance of conscious intention to initiate a motor action. This signal of cerebral activation recorded by the RP is considered to be arising from the supplementary motor area (SMA; Deecke & Kornhuber, 1978; Lang, Zilch, Koska, Lindinger, & Deecke, 1989). More recently, Haggard and Eimer (1999) recorded both RP and the lateralized readiness potential (LRP) while subjects performed M and W judgements in two different experimental conditions: (1) fixed movement (performing movement with the same hand in each experimental block) and (2) free choice condition (subjects freely decided in each trial which hand to use to perform the movement). The authors found a covariation between W judgement and the onset of the LRP, while no correlation was found with the onset of RP. This result has been interpreted in the view that the conscious intention to move reflects the neural activity related to the selection of a specific movement and not to an abstract representation of action (prior intention). Following this model, conscious intention occurs after the stage of movement selection (see Figure 2.2; C ¼ urge to move). In summary, the results of the electrophysiological studies mentioned above suggest that SMA is crucial for the awareness of the intention to move. Functional MRI experiments, in which self-initiated and externally triggered movements were compared, support this hypothesis (Cunnington,
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C Urge to move
D
Planner (movement selection)
Goals/ Prior intention
A
B
Motor monitoring system (Comparator)
Forward model (Movement predictor)
Limb
World
Efference copy
E Sense of agency
Sensory information
Figure 2.2 A modified version of the forward model of motor production (From Haggard, 2005, with permission from Elsevier, Trends in Cognitive Science, 9(6), 290–295.) and motor control (From Berti & Pia, 2006, with permission from Wiley InterScience, Current Directions in Psychological Science, 15(5), 245–250.)
Windischberger, Deecke, & Moser, 2002; Jahanshahi et al., 1995; Jenkins, Jahanshahi, Jueptner, Passingham, & Brooks, 2000). More recently, in an fMRI study Lau and colleagues (2004), using Libet’s paradigm, found activations in the pre-SMA, the dorsolateral prefrontal cortex (DPFC or Brodmann’s area 46), and in the intraparietal sulcus when normal healthy subjects attended to their intentions. The relevance of SMA and pre-SMA is also corroborated by the anatomical lesional data. Berti et al. (2005) found that both these areas are generally spared in hemiplegic patients with anosognosia, suggesting that in such patients representation of the intended motor act it is still possible, although distorted. Thus, in anosognosic patients the intentional system and probably the feed-forward model appear to still be preserved, and possibly unawareness for hemiplegia is caused by a damage of the comparator (see lesion of A in Figure 2.2). To further support this hypothesis, Berti et al. (2007) compared the muscle electric activity (recorded using surface electromyogram: EMG) in the left and right upper trapezius of one patient with hemiplegia (case CR) and a dense anosognosia (Bisiach Standard Neurological Examination score: 3/3), one patient with hemiplegia without anosognosia (case SF), and one healthy control. There were three experimental conditions: (1) reaching with the left hemiplegic limb; (2) reaching with the right limb; and (3) resting condition. Detection of the activation of the proximal muscles on both sides for reaching movement with the left hemiplegic arm could be considered an indirect evidence of the preserved intention to move. This hypothesis was confirmed as in patient CR a preserved activity in the left proximal muscle despite the presence of anosognosia has been found. The authors suggested that the differences between the two patients SF and CR
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could concern the dysfunctioning comparator in CR, demonstrating that motor intention is still preserved. To verify the Frith et al. (2000) hypothesis that the nonveridical awareness of action is based on the dominance of motor planning (forward model) on the somatosensory feedback, Fotopoulou et al. (2008) studied four patients with motor anosognosia and four with hemiplegia without anosognosia. They manipulated both intention to move and visual feedback of movement using a rubber hand. The visual feedback could be coherent or incoherent with respect to the intention to move modulated by different instructions: (1) perform a selfgenerated movement; (2) patients were told that an experimenter would lift his left arm (externally generated movement); and (3) no movement required. Dependent variables were the movement detection and the agency score. Anosognosic patients showed a comparable performance with controls in all conditions with the exception of the first condition (self-generated movement performance) while an incoherent feedback was provided (no rubber hand movement). Anosognosic subjects ignored the incoherent visual feedback (the rubber hand was not moving) only in the condition in which they intended to move. On the other hand, in the externally generated movement they performed correctly, demonstrating that anosognosic patients ignore the visual information (sensory feedback) only in the condition implying the intention to move. These results are compatible with the Frith et al. (2000) hypothesis that the nonveridical awareness of movement ‘‘is created on the basis of a comparison between the intended and predicted position of the limbs, and not on the basis of a mismatch between the predicted and actual sensory feedback’’ (Fotopoulou et al., 2008).
Effect of Caloric Vestibular Stimulation on Neglect and Related Disorders It is well known that cold caloric vestibular stimulation (CVS) may produce a transient (nearly 15–20 minutes) recovery of extrapersonal (Cappa et al., 1987; Rubens, 1985; Silberpfennig, 1941), personal (Cappa et al., 1987; Rode et al., 1992), representational neglect (Geminiani & Bottini, 1992; Rode & Perenin, 1994) and of several related disorders such as anosognosia for hemiplegia (Cappa et al., 1987; Rode et al., 1992), somatoparaphrenia (Bisiach, Rusconi, & Vallar, 1991; Rode et al., 1992), somatosensory (Vallar, Bottini, Rusconi, & Sterzi, 1993; Vallar et al., 1990), and motor deficits (Rode et al., 1992; see also Rossetti & Rode, 2002 and their Table 1 for a review of the effect of CVS on different neglect symptoms). Caloric vestibular stimulation consists of an iced water irrigation of the external ear canal contralateral to the brain lesion. The injection determines an ocular reflex (slow-phase nystagmus) toward the stimulated ear and sometimes may induce negative sensations, such as nausea, vomiting, and dizziness.
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Table 2.1 Positive and Negative Effects of CVS as a Function of the Side of Stimulation (Left or Right Ear) and Water Temperature (Cold or Warm Water) in RBD Patients
Cold water Warm water
Left-Ear CVS
Right-Ear CVS
Leftward nystagmus improvement of the deficit Rightward nystagmus worsening of the deficit
Rightward nystagmus worsening of the deficit Leftward nystagmus improvement of the deficit
CVS, Caloric vestibular stimulation; RBD, right brain damaged.
During CVS the experimenter may vary the side of stimulation (ipsilesional or contralesional ear) and the water temperature (cold or warm water). The interaction of these two factors induces different physiological changes (direction of slow-phase nystagmus) and as a consequence positive or negative effects on the deficit. In fact, in right brain–damaged (RBD) patients, the irrigation of the contralesional ear with cold water (left CVS) or the irrigation of the ipsilesional ear with warm water, both producing a leftward slow-phase nystagmus, induces an improvement of neglect. Conversely, the irrigation of the ipsilesional ear (right CVS) with cold water or the irrigation of the contralateral ear (left CVS) with warm water produces a rightward slow phase nystagmus and induces a worsening of these symptoms (Rubens, 1985; see Table 2.1). As mentioned above, CVS may produce a temporary recovery of some neurological deficits such as hemianesthesia, namely the impaired detection of tactile stimuli delivered on the side of the body contralateral to a brain lesion (Bottini et al., 2005; Vallar et al., 1993; Vallar et al., 1990). The effect of CVS on an apparently elementary deficit suggests that the right hemisphere may have a role on conscious tactile perception. In RBD patients, left CVS (cold vestibular stimulation in the left ear) induces a transient improvement of left tactile perception (Bottini et al., 2005; Vallar et al., 1990; Vallar et al., 1993). Conversely, in left brain–damaged patients (LBD) right CVS (cold vestibular stimulation in the right ear) does not modulate right hemianesthesia. The only exception is represented by the few cases of LBD patients presenting right hemineglect (Vallar et al., 1993; for an extensive review of the effects of CVS on somatosensory processing, see Vallar, 1997). The observation of this hemispheric asymmetry suggested that left hemianesthesia also contains a ‘‘nonsensory or perceptual component’’ (Vallar et al., 1993), responsible for the access to conscious awareness of tactile stimuli, which is strictly related to neglect and may be positively modulated by CVS (Vallar et al., 1993). Conversely, right hemianesthesia associated with lesion of the left hemisphere could reflect a mainly primary (elementary) sensory deficit. This hypothesis has been supported by different neurophysiological (Vallar, Bottini, Sterzi, Passerini, & Rusconi, 1991; Vallar, Sandroni, Rusconi, & Barbieri, 1991) and clinical (Smania & Aglioti, 1995; Sterzi et al., 1993) evidence.
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SPN
SPN
SPN
L
R (a) left cold CVS
(b) left cold CVS
(c) right cold CVS
Figure 2.3 Effects of cold caloric vestibular stimulation (CVS) on tactile hemianesthesia in right brain–damaged and left brain–damaged patients as a consequence of the stimulation side (contralesional versus ipsilesional ear stimulation). The damaged hemisphere is colored in black. L, left; R, right; SPN, slow-phase nystagmus; green: positive effect (recovery) of tactile perception; red: no effect on tactile perception. (See Color Plate 2.3)
To better clarify this hemispheric asymmetry, Bottini et al. (2005) systematically studied the effect of CVS on RBD and LBD hemianesthetic patients (Bottini et al., 2005). The authors confirmed previous evidence of an improvement of tactile perception after left cold CVS in RBD patients (a) and the absence of positive effects after right cold CVS on LBD subjects (c). Interestingly, they also described a significant remission of right hemianesthesia when the left ipsilesional ear was stimulated in LBD patients (b) (see Figure 2.3). The authors also studied an LDB patient with fMRI before and after CVS and a group of healthy subjects during a tactile perception task. They found that recovery of tactile perception after CVS was associated with neural activity in patient’s right secondary somatosensory cortex (SII). In the control subjects the activation of SII for ipsilateral stimuli was of a greater extent in the right hemisphere for right touches than in the left hemisphere for left touches (right SII–right stimuli, left SII–left stimuli). These results suggest a right hemispheric specialization for the body representation (in particular for the hand representation) and that this hemisphere contains a more complete representation of the whole body space compared with the left hemisphere (Bottini et al., 2005).
Recovery of Anosognosia for Hemiplegia after Caloric Vestibular Stimulation The effects of caloric vestibular stimulation on RBD patients unaware of their left hemiplegia were first described by Cappa and colleagues (1987), who used this method on four patients with severe neglect and anosognosia for both motor (upper and lower limbs) and visual deficits. In two cases, anosognosia was not affected by the manipulation, while in the other two patients cold left CVS provoked a transient remission of this disorder immediately after the stimulation. Vallar et al. (1990) observed a temporary amelioration of hemianesthesia
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after CVS in three patients and, in one of these, they also reported a temporary complete remission of extrapersonal, personal neglect and anosognosia. Bisiach et al. (1991) described a patient suffering from a right fronto-temporo-parietal stroke showing anosognosia with somatoparaphrenic delusions who underwent CVS three times; after all the trials he completely recovered from his somatoparaphrenic delusion, which reappeared with the same characteristics in about 2 hours, demonstrating the possible modulation of a body scheme disorder by a peripheral stimulation. Rode et al. (1992) found the same results applying CVS on a somatoparaphrenic and long-lasting anosognosic patient with a severe hemiplegia and hemianopia caused by a large cortico-subcortical infarction in the right brain hemisphere involving the parieto-temporo-occipital carrefour. After the left ear canal irrigation with iced water, a dramatic recovery of both anosognosia and somatoparaphrenia was reported and, surprisingly, CVS also caused a reduction of the left motor deficit. Geminiani and Bottini (1992) observed the effect of CVS in RBD patients. In one patient with slight personal neglect and moderate anosognosia, vestibular stimulation caused personal neglect to temporarily disappear but anosognosia remained unchanged. In two other cases, CVS produced a temporary amelioration of, respectively, a moderate and severe anosognosia (Geminiani & Bottini, 1992). Ramachandran (1995) used CVS on a woman with a severe left neglect syndrome and a dense left hemiplegia of which she was totally unaware. Furthermore, when asked about whose hand was her left one, she showed a clear ‘‘feeling of non belonging’’ of her left arm, which she attributed either to the experimenter or to her son (Ramachandran, 1995, p. 27 ). After the irrigation of the left canal ear with 10cc of iced water and the appearance of the nystagmus, the patient was assessed for the awareness of the motor deficit and the sense of limb ownership, showing a full recovery from both these conditions. The relationship between recovery of motor deficits and improvement of anosognosia has been more systematically investigated by Rode et al. (1998), who studied the effect of vestibular stimulation comparatively in two groups of hemiplegic patients: (1) three RBD patients with neglect without anosognosia and six with neglect and anosognosia; and (2) nine LBD patients without neglect. In contrast to the LBD group, motor performance in the RBD group significantly improved after CVS, and a temporary remission of personal neglect and anosognosia was also observed in 5 out of 6 patients (Rode et al., 1998). Vallar et al. (2003) replicated the same results in a group of four RBD patients with neglect, hemianopia, hemianesthesia, and hemiplegia of the left upper limb showing anosognosia for the motor defect. The stimulation with iced water temporarily improved motor strength together with a recovery from the unawareness deficit (Vallar et al., 2003). Taken together, these observations suggest that CVS can have a positive effect on both motor deficit itself and anosognosia for hemiplegia. This evidence may argue for a nonprimary,
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higher-order motor neglect component in patients’ hemiplegia; furthermore, it is worth noting, even if counterintuitive, that the less severe the deficit, the more aware of it the patient seems to become (Vallar et al., 2003). These findings suggest that anosognosia might not relate to a primary deficit but to a higherlevel disorder such as a ‘‘deficit of motor intention or planning’’ (Vallar et al., 2003) and that the positive effects of the stimulation on both hemiplegia and anosognosia could be due to the possible amelioration of this intentional motor deficit (Vallar et al., 2003). We may speculate that another possible interpretation is that CVS may restore the space and body schema representation and therefore rebalance the predicted and the actual state components of Frith’s model of anosognosia (Frith et al., 2000).
Conclusion In our opinion the main outstanding questions relative to the pathological mechanisms underpinning anosognosia are as follows: 1. The role of the intention to move: in other words is the denial of hemiplegia due to the fact that patients with this symptom do not have the intention to move the plegic limb, not even to trigger the cognitive procedures to plan and perform the movement? In some patients, not all of them anosognosic subjects, the presence of a motor neglect component could explain this deficit denial (Vallar et al., 2003). Nevertheless, recent experiments on anosognosic patients seem to show that the intention to move is still preserved (Berti et al., 2007; Fotopoulou et al., 2008). Furthermore, this theory does not fully explain why there are anosognosic patients that do not show motor neglect, and why there are some patients that claim to have performed the movement when the movement has not actually occurred (Frith et al., 2000). We call this clinical manifestation as a form of delusional/nonveridical awareness/productive anosognosia. 2. The role of damage at different levels of the motor control system. We assume that anosognosia may be generated by a dysfunction of the comparator as described by the Frith et al., model (2000). In this case the patients are still able to compare desired and predicted states, but the discrepancies between predicted and actual states are ignored. Frith proposes that this happens because the sensory feedback is not available or neglected, inducing an overcoming of the prediction on the afferent information. This hypothesis better explains the delusional anosognosia, and it also explains some interesting aspects of the modulation of anosognosia through the vestibular caloric stimulation (Cappa et al., 1987; Vallar et al., 2003). One may speculate that vestibular stimulation transiently recovers the somatosensory afferents, rebalancing the predicted and the actual state components in the model, temporarily resolving the overcoming of the former on the latter. The role of the comparator in generating anosognosia remains to be clarified.
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3. Focusing on the anatomical correlates of anosognosia, the feed-forward model and the feedback theory make different anatomical predictions. The debate is still open on the crucial localization of anosognosia in the parietal or in the motor cortices.
Observation of anosognosic patients (Bisiach et al., 1986; Ramachandran, 1995; Vallar et al., 2003) indicates that there are diverse manifestations that suggest not only different degrees of severity of motor denial (quantitative index) but also a qualitative/functional difference among these symptoms (qualitative/functional indexes)—some of them being more negative/defective, others more positive/productive. In the future, a more detailed investigation of these symptoms could probably lead to a multifaceted classification, including different kinds of motor denial. References Adair, J. C., Gilmore, R. L., Fennell, E. B., Gold, M., & Heilman, K. M. (1995). Anosognosia during intracarotid barbiturate anesthesia: Unawareness or amnesia for weakness. Neurology, 45(2), 241–243. Adair, J. C., Schwartz, R. L., Na, D. L., Fennell, E., Gilmore, R. L., & Heilman, K. M. (1997). Anosognosia: Examining the disconnection hypothesis. Journal of Neurology, Neurosurgery and Psychiatry, 63(6), 798–800. Appelros, P., Karlsson, G. M., & Hennerdal, S. (2007). Anosognosia versus unilateral neglect. Coexistence and their relations to age, stroke severity, lesion site and cognition. European Journal of Neurology, 14(1), 54–59. Babinski, J. (1914). Contribution a` l’etude des troubles mentaux dans l’hemiplegie organique cerebrale (anosognosie). Revue Neurologique, 27, 845–848. Babinski, J. (1918). Anosognosie. Revue Neurologique (Paris), 31, 365–367. Barkman, A. (1925). De l’anosognosie dans l’emiplegie cerebrale: Contribution a l’etude de ce symptome. Acta Medica Scandinavica, 62, 235–254. Berti, A., Bottini, G., Gandola, M., Pia, L., Smania, N., Stracciari, A., et al. (2005). Shared cortical anatomy for motor awareness and motor control. Science, 309(5733), 488–491. Berti, A., Ladavas, E., & Della Corte, M. (1996). Anosognosia for hemiplegia, neglect dyslexia, and drawing neglect: Clinical findings and theoretical considerations. Journal of the International Neuropsychological Society, 2(5), 426–440. Berti, A., Ladavas, E., Stracciari, A., Giannarelli, C., & Ossola, A. (1998). Anosognosia for motor impairment and dissociations with patient’s evaluation of the disorders: Theoretical considerations. Cognitive Neuropsychiatry, 3, 21–44. Berti, A., & Pia, L. (2006). Understanding motor awareness through normal and pathological behavior. Current Directions in Psychological Science, 15(5), 245–250. Berti, A., Spinazzola, L., Pia, L., & Rabuffetti, M. (2007). Motor awareness and motor intention in anosognosia for hemiplegia. In P. Haggard, Y. Rossetti, & M. Kawato (Eds.), Sensorimotor foundations of higher cognition series: Attention and performance number XXII (pp. 163–182.). New York: Oxford University Press. Bisiach, E. (1995). Unawareness of unilateral neurological impairment and disordered representation of one side of the body. Higher Brain Function Research, 15(2), 113–140.
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3
Anosognosia for Hemiparesis and Hemiplegia: Disturbed Sense of Agency and Body Ownership Hans-Otto Karnath and Bernhard Baier
Normally, we are aware that our arms and legs belong to us and not to someone else. When resting, we are aware that our limbs do not move, and when moving, we realize that our limbs cause the action. This natural knowledge is based on a self-awareness, a sense of being us. It allows us to discriminate between our own body and the bodies of other people, and to attribute an action to ourselves rather than to another person. Some of the most challenging questions in cognitive science and in philosophy are, How does this sense arise? How does it function? What mechanisms are involved? How can a subject determine the proper origin of an action or a body part? How is one able to attribute the agent of an action or a body part to oneself? Recent studies addressed these questions experimentally by using different technical approaches. For example, behavioral investigations in healthy subjects studied the mechanisms underlying the rubber hand illusion (Botvinick & Cohen, 1998; Ehrsson, Holmes, & Passingham, 2005; Ehrsson, Spence, & Passingham, 2004; Ehrsson, Wiech, Weiskopf, Dolan, & Passingham, 2007; Moseley et al., 2008; Tsakiris & Haggard, 2005). Watching a rubber hand being stroked synchronously with one’s own (unseen) hand causes a phenomenal incorporation of the rubber hand; the rubber hand is experienced as part of one’s own body. Studying the conditions evoking the illusion allows insights into the processes related to our feeling of body ownership. The sense of body ownership and the awareness of being causally involved in an action—the sense of agency—have also been investigated by using functional neuroimaging methods (Farrer et al., 2003; Tsakiris, Hesse, Boy, Haggard, & Fink, 2007a). A further approach is the study of neurological patients showing specific disturbances of 39
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these senses after brain damage. Stroke patients with so-called anosognosia for hemiparesis or for hemiplegia (AHP) typically deny the weakness of their paretic or plegic limb(s) and are convinced that they move properly. Stroke patients may also show a disturbed sense of ownership (DSO) with respect to the paretic/ plegic limb(s). They experience their limb(s) as not belonging to them and may even attribute them to other persons. This chapter will provide an overview of recent clinical and anatomical findings in patients with AHP. Interestingly, disturbed beliefs about the functioning of one’s own limbs (the sense of agency) and disturbed feelings of limb ownership (the sense of ownership) appear to be closely linked, both clinically and anatomically. It appears that the right insula may play a central role for both senses. We will argue that the right insula may be a central node of the network involved in human body scheme representation.
Anosognosia for Hemiparesis/-plegia Disturbed Sense of Agency The characteristic feature of stroke patients with AHP is their false belief that they are not paralyzed. Their feeling of being versus not being causally involved in an action—their sense of agency—is dramatically disturbed. Despite the very obvious fact that the contralesional arm, leg, and/or face are plegic or severely paretic, these patients behave as though the disorder does not exist. Anton (1893) was the first to describe a patient, Wilhelm H., with a left-sided hemiparesis who did not recognize his weakness. Patients such as Wilhelm H. are convinced that their paretic/plegic limbs function normally. When asked to move the paretic/plegic arm or leg, they may do nothing or may move the limb of the opposite side. However, in both situations they are either convinced that they have successfully executed the task or may argue that they can move in a generic manner. Some patients may not even experience their paresis/plegia when confronted with facts that unambiguously prove the disorder. For example, when asked to clap their hands, no sound is heard due to the paresis/plegia of one arm. Even under these conditions, such patients are not able to correct their feeling of being involved in an action. Often, the patients comment on the apparent inability to move their arm or leg with confabulations such as ‘‘My leg is tired’’ or ‘‘My arm is lazy.’’ When directly asked for the reason of not having moved the contralesional limb(s), such patients might respond: ‘‘I could walk at home, but not here. It’s slippery here’’ (Nathanson, Bergman, & Gordon, 1952). Patients might argue that the arm ‘‘is too stiff, due to the cold’’ or that ‘‘somebody having a hold of the arm’’ keeps the arm from moving (Nathanson et al., 1952).
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Disturbed Sense of Ownership In the normal experience of an action, the sense of agency and the sense of ownership coincide and are inseparable, though different sources generating these senses have been assumed (Gallagher, 2000; Haggard, 2005; Tsakiris, Sch€ utz-Bosbach, & Gallagher, 2007b; Wolpert, 1997). Therefore, it is interesting to know whether in neurological patients with brain damage a disturbed feeling of being causally involved in an action typically is associated or dissociated from a disturbed feeling of body ownership. Are both senses represented in common or rather separate neural systems? Indeed, previous studies indicated that the false belief of not being paralyzed in patients with AHP may be associated with other abnormal attitudes toward and/or perceptions of the paretic/plegic limb(s) (Cutting, 1978; Feinberg, Roane, & Ali, 2000; Meador, Loring, Feinberg, Lee, & Nichols, 2000; Stone, Halligan, & Greenwood, 1993). Cutting (1978) referred to them as ‘‘anosognosic phenomena.’’ Patients may experience their limb(s) as not belonging to them or as missing (asomatognosia), or may even attribute them to other persons (somatoparaphrenia). Both of these misbeliefs have a common characteristic, namely that the subjects experience a disturbed sense of ownership of their contralateral limb(s). They are convinced that this is not their own arm and/or leg. Thus, it has been suggested to unify these phenomena under the term ‘‘disturbed sensation of limb ownership’’ (DSO) (Figure 3.1; see also subsequent paragraphs). Other phenomena observed were ‘‘anosodiaphoria’’ (patients considering their paresis/plegia as harmless, i.e., are not appropriately concerned about it), ‘‘misoplegia’’ (patients expressing negative feelings about their paretic/ plegic limbs), ‘‘personification’’ (patients giving names to their limbs), ‘‘kinaesthetic hallucinations’’ (the illusion that the paretic/plegic limb is moving as if controlled by an invisible force), or ‘‘supernumerary phantom limb’’ (patients’ belief that a new, intact limb has appeared). Although ‘‘anosognosic phenomena’’ and the false belief of not being paralyzed were regarded to be associated in some way (Feinberg et al., 2000), it is not clear how tightly these phenomena are linked. Some studies found a strong association between a disturbed feeling of being involved in a limb movement and the experience that this limb is not belonging to one’s body (Feinberg et al., 2000; Meador et al., 2000). Meador et al.’s data (2000) revealed an association close to 70% between the two phenomena in patients who underwent diagnostic intracarotid amobarbital inactivation of the right cerebral hemisphere. In contrast, Cutting (1978) observed that 29% of his patients with left hemiplegia showed such ‘‘anosognosic phenomena’’ without having the false belief of not being paralyzed, while only 8% exhibited both phenomena. A recent study reassessed this issue in a large sample of 79 acute stroke patients with right brain damage and hemiparesis/-plegia (Baier & Karnath, 2008). The authors systematically examined both phenomena, the experience
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of being involved in an action, as well as the presence of various ‘‘anosognosic phenomena.’’ Their particular focus was on the occurrence of a disturbed sensation of limb ownership (DSO). The authors found a false belief of not being paralyzed in about 15% of their patient sample. Interestingly, all but one (92%) of these patients also showed a DSO for their contralesional limb(s) (see Figure 3.1). No other subjects in the sample of 79 patients exhibited DSO. Baier and Karnath (2008) thus concluded that a disturbed sense of limb ownership obviously is a characteristic feature of AHP. If this surprising finding should be confirmed by future work, it would indicate that our sense of being involved in an action and our sense of ownership with respect to this limb not only are tightly linked phenomena in the normal experience of an action but also in the case of their disturbance after brain injury. Two of the patients with DSO from the sample of Baier and Karnath (2008) attributed their limb to their wife, three to the examiner, and one to their room neighbor. Traditionally, such beliefs were termed ‘‘somatoparaphrenia.’’ Five further patients with DSO from this sample neither attributed their limb to
Figure 3.1 Percentage of additional disturbance of sensing limb ownership (DSO) as well as other abnormal attitudes toward and/or perceptions of the paretic/plegic limb(s) found in a continuously admitted sample of patients with anosognosia for hemiparesis/-plegia (AHP). Asomatognosia and somatoparaphrenia have the common characteristic that the subjects experience a disturbed ownership of their contralatateral limb(s). Both misbeliefs thus were combined and illustrated as ‘‘disturbed sensation of limb ownership (DSO).’’ All but one (92%) of the patients with AHP also showed DSO. The finding argued for a tight link between our sense of agency and our sense of limb ownership. (Adapted from Baier & Karnath, 2008, with permission from the American Heart Association, Stroke, 39, 486–488.)
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themselves nor to somebody else—traditionally labeled as ‘‘asomatognosia.’’ Nevertheless, also the latter group of patients had the feeling that their limb somehow belonged to another person. When they were asked whether their limb belonged to another person, none of them clearly denied that it did not belong to somebody else. Answers were given such as ‘‘I don’t know,’’ ‘‘I’m not sure,’’ ‘‘I don’t think so,’’ etc. On the other hand, the patients with so-called somatoparaphrenia used terms like ‘‘perhaps’’ or ‘‘believe’’ when they attributed their limb to a specific person. This led the authors to suggest that these misbeliefs do not necessarily correspond to two distinct phenomena (Baier & Karnath, 2008). Rather, it seems that there is a continuum of conviction that the limb does not belong to one’s own body but to someone else. ‘‘Disturbed sensation of limb ownership (DSO)’’thus appeared to be a more appropriate term to describe these feelings.
Normal or Pathological? Criteria to Assess the Disturbed Senses Clinically, AHP and DSO are not trivial problems. A failure to realize a paresis of one’s own extremities may delay medical consultation after a stroke (GhikaSchmid, van Melle, Guex, & Bogousslavsky, 1999). Also, such patients are often reluctant to enroll in rehabilitation programs (Appelros, Karlsson, Seiger, & Nydevik, 2002; Hartman-Maeir, Soroker, & Katz, 2001). Thus, a reliable diagnosis of the disorder as soon as possible after onset is desired. However, to date some inconsistencies in diagnosing the misbeliefs still seem to exist between different investigators. Consequently, widely varying incidence rates have been reported for AHP in acute stroke patients, ranging from 7% to 77% (for review, see Orfei et al., 2007). This variation points to a central question: What exactly do we mean when we talk about AHP? Shall we already consider a patient as ‘‘anosognosic’’ if he or she does not spontaneously mention the deficit in a conversation with the examiner? Indeed, according to Bisiach et al.’s anosognosia scale (1986) patients should be considered to have ‘‘mild anosognosia’’ when they do not acknowledge their hemiparesis spontaneously following a general question about their complaints. However, the question arises whether there are ‘‘normal,’’ that is, nonpathological explanations for not addressing a deficit after such a general question. A recent study investigated this question (Baier & Karnath, 2005). The authors examined 128 acute stroke patients for AHP by applying the anosognosia scale of Bisiach et al. (1986). They closely analyzed the motives and the explanations given by those patients who did not acknowledge their hemiparesis spontaneously, that is, who traditionally would have been diagnosed showing at least ‘‘mild AHP.’’ The authors detected that 94% of these patients suffered from other neurological deficits in addition to their paresis/plegia. Following a general question about their complaints, they mentioned these deficits instead of limb
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paresis/plegia. However, the same patients immediately acknowledged their paresis/plegia when the examiner addressed the strength of their limbs. Baier and Karnath (2005) thus concluded that a reason for not mentioning a paresis/ plegia after a first, general question could be that other, additional deficits have a higher impact for these subjects after stroke. The authors argued that such behavior is reasonable and thus should not be diagnosed as ‘‘anosognosia.’’ With respect to the anosognosia scale of Bisiach et al. (1986), they suggested that only patients with grade 2 (the disorder is acknowledged only after demonstrations through routine techniques of neurological examination) and grade 3 (no acknowledgement of the disorder can be obtained) should be labeled as AHP (see Table 3.1). If this criterion is used, comparable incidence rates between 10% and 18% are observed for AHP in unselected samples of acute, hemiparetic stroke patients (Appelros et al., 2002; Baier & Karnath, 2005, 2008; Starkstein, Fedoroff, Price, Leiguarda, & Robinson, 1992). Since patients with a disturbed sense about the functioning of body parts often exhibit additional DSO for their contralesional limb(s), a clinical exam of stroke patients with hemiparesis/-plegia should combine both aspects (see Tables 3.1 and 3.2). Beyond these aspects, the questionnaire illustrated in Table 3.2 also explores whether a subject has a lack of appropriate concern of the paretic/plegic limbs (anosodiaphoria); expresses negative feelings, for example, hatred, for his or her limb (misoplegia); gives his or her limbs names (personification); feels his or her limbs moving automatically (kinesthetic hallucinations); or is convinced that a new, intact limb has appeared (supernumerary phantom limb).
Table 3.1 Clinical Scale to Test for a Disturbed Belief about the Functioning of One’s Own Limbs (Sense of Agency) No Anosognosia • The disorder is spontaneously reported or mentioned by the patient following a general question about his or her complaints. (former grade 0 by Bisiach et al., 1986) • The disorder is reported only following a specific question about the strength of the patient’s limbs. (former grade 1 by Bisiach et al., 1986) Anosognosia—Grade I
• The disorder is acknowledged only after demonstrations through routine techniques of neurological examination. (former grade 2 by Bisiach et al., 1986) Anosognosia—Grade II
• No acknowledgement of the disorder is obtained. (former grade 3 by Bisiach et al., 1986) Source: From Baier & Karnath, 2005. This table is a modified version of the anosognosia scale suggested by Bisiach and colleagues (1986).
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Table 3.2 Questionnaire to Test for a Disturbed Sense of Limb Ownership (DSO) as Well as for Other Abnormal Attitudes toward and/or Perceptions of Paretic/Plegic Limbs Disturbed sense of limb ownership (DSO)
Is this your arm/leg? (combined with pointing or elevating the arm/leg) [aspect: asomatognosia] To whom belongs this arm/leg? (combined with pointing or elevating the arm/leg) [aspect: somatoparaphrenia]
Anosodiaphoria
Does the weakness of your arm/leg represent a strong impairment or just a minor issue, which is not important to you?
Misoplegia
Do you have any emotions for your arm/leg? Do you hate or deny your arm/leg?
Personification
Does your arm/leg have a name? Have you ever given your leg/arm a name?
Kinesthetic hallucinations
Have you ever had the impression that your arm/leg moves without your own will, i.e., without you having moved it/having initiated the movement? Does your arm/leg move as if controlled by an invisible hand?
Supernumerary phantom limb
How many arms/legs do you have? Do you have the feeling that you have another arm/leg beyond the two arms/legs that you have since birth?
Source: From Baier & Karnath, 2008.
Pathogenetic Models The pathogenesis of AHP continues to be a subject of controversy. Early investigators like Anton (1893) and Babinski (1914) emphasized the importance of hemisensory loss, particularly the loss of proprioception for the genesis of the disorder. The loss of sensory feedback would induce the patient’s unawareness of the contralateral limb function. Levine, Calvanio, and Rinn (1991) postulated that in the absence of somatosensory and proprioceptive input, the patient does not have immediate knowledge that his or her limb has moved or not moved but rather must discover the paresis/plegia by observing his or her own failure in tasks requiring movement of the affected limb. General intellectual impairment or spatial neglect might prevent this discovery. Other models considered AHP as a defect of neural awareness systems (McGlynn & Schacter, 1989), an overestimation of self-performance, lack of mental flexibility, inability to integrate episodic awareness into generic knowledge (Marcel, Tegner, & Nimmo-Smith, 2004), or a psychological defense mechanism manifesting ‘‘the patient’s drive to be well’’ when he or she is facing a sudden and threatening reality such as hemiparesis/-plegia after stroke (Weinstein & Kahn, 1955). Carruthers (2008) claimed that patients with AHP might have an impaired ‘‘online’’ representation
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of their body (what the body is currently like) due to a lack of access to an updated ‘‘offline’’ representation of the body (the state of what the body is usually like). New information from the body has not been integrated since the patient was paralyzed. The patient’s access to the erroneous ‘‘offline’’ representation makes the patient feel embodied as he or she was before the paresis. Several authors have focused on processes involved in motor planning and motor control to explain the disorder. According to the feed-forward model suggested by Heilman (1991), weakness of a limb is recognized when a mismatch is detected between an intended movement and the actual motor performance. A module comparing intended and observed movements notes possible discrepancies. Patients with AHP do not intend to move. As a consequence, no mismatch is generated in the comparator module and the patient does not recognize his or her paresis. Berti and Pia (2006) proposed a modification of this hypothesis, suggesting that in AHP the comparator module itself is deficient. A further model by Frith, Blakemore, and Wolpert (2000) assumed that awareness of the current and possible states of the motor system are based on sensory information from the muscles, the skin, and the motor command stream. Awareness of initiating a movement is based on a representation of the predicted consequences of making that movement. In patients with AHP, the representations of the desired and the predicted positions of the limb are intact, inducing the normal experience of initiating a movement. However, according to Frith and colleagues, these patients are not aware of the actual limb position. Due to a loss of sensory feedback (by damage of the relevant brain regions or by spatial neglect), information about the actual position of the limb indicating that no motor action has occurred is not available. AHP thus is assumed to result from the lack of experiencing a discrepancy between intended and predicted positions, based on the unawareness of the actual state of the limb. As a result, a successful motor action is pretended and a false experience of movement is induced. A first direct experimental investigation of this hypothesis has recently been undertaken by Fotopoulou et al. (2008).
Anatomy of Anosognosia for Hemiparesis or Hemiplegia: The Neural Correlates of Disturbed Experience of One’s Own Limbs and Actions Disturbed Sense of Agency The neural correlates of the patient’s false belief of not being paralyzed despite obvious hemiparesis/-plegia is also a matter of considerable debate. Lesions of various brain areas such as parietal, temporal and frontal cortex, the thalamus, corona radiate, basal ganglia, internal capsule, and pons were suggested to
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evoke AHP (Bakchine, Crassard, & Seilhan, 1997; Bisiach et al., 1986; Ellis & Small, 1997; Evyapan & Kumral, 1999; Levine et al., 1991; Maeshima et al., 1997; Starkstein et al., 1992). Consistently, several studies have observed large lesions in the territory of the middle cerebral artery of the nondominant hemisphere to be associated with the disorder. Bisiach and colleagues (1986) assumed that large lesions encompassing the right infero-posterior parietal regions as well as the right thalamus and/or the lenticular nucleus lead to a disturbed feeling of being causally involved in an action. Another group study compared 30 acute stroke patients with AHP and 10 patients with hemiplegia and spatial neglect but no AHP (Ellis & Small, 1997). The patients with AHP had right-sided lesions, in particular in the deep white matter, the basal ganglia, the thalamus, and the insula, whereas both patient groups had lesions of frontal areas, especially the premotor, Rolandic, and paraventricular regions. The authors concluded that AHP is due to damage of neuronal circuits involving the basal ganglia, leading to an inflexibility of the response to the lack of movement in a paretic/plegic limb. A recent review of 23 single case and group studies revealed that among the 83 reported patients with AHP, 44 patients had lesions of the frontal lobe and/or the parietal lobe, 31 patients of the temporal lobe and 12 patients of the occipital lobe (Pia, Neppi-Modona, Ricci, & Berti, 2004). Only 17 patients were reported with a lesion restricted to a single cortical area, whereas in 45 cases more than one cortical lobe was involved. With regard to subcortical structures, 34 out of the 83 patients with AHP had subcortical lesions. The basal ganglia (22 patients), the insula (19 patients), and the internal capsule (18 patients) were the most frequently affected subcortical structures. Recently, new tools have been developed that allow more precise lesion localization in humans (for a review, see Rorden & Karnath, 2004). These techniques reduce significantly the uncertainty brought in by the procedures used in previous anatomical studies where only rough anatomical landmarks could be taken into consideration, where lesion documentation still was based on a paper-and-pencil basis, where only a rather small number of patients was included, and no direct visual and/or statistical comparisons between patients with and without a disturbed sense of agency was carried out. In contrast, the new techniques can use the entire lesioned area of each individual subject for a high-resolution analysis (Rorden & Karnath, 2004). Different procedures have been developed that allow voxelwise statistical comparisons between anatomical groups. Such voxelwise lesion-behavior mapping (VLBM) techniques differ in major respects but share the idea of comparing the performance of individuals with injury to a voxel to the performance of individuals where that voxel is not injured (Rorden, Fridriksson, & Karnath, 2009; Rorden, Karnath, & Bonilha, 2007). Voxelwise lesion-behavior mapping techniques detect brain regions that predict poor performance when injured and good performance when spared (see Box 3.1).
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THE STUDY OF ANOSOGNOSIA
Box 3.1 An illustration of the importance of using control groups in lesion studies
A
Hemianopia (N=36)
V1
No hemianopia (N=104)
B
Subtraction analysis
C
VLBM analysis
25
CHi
45
Consider that we are interested in identifying primary visual cortex in humans. In order to identify the relevant brain region, we explore the anatomy correlated with a complete loss of primary vision for the left visual half-field, following a unilateral, right-hemisphere stroke. (A) The top row shows a classical lesion overlay plot for 36 consecutively admitted patients with left-sided visual field cuts following a right-sided lesion. This panel highlights damage to the subcortical white matter extending to the cortical temporoparietal junction (TPJ). The conclusion from this lesion overlay plot would be that primary vision in the left visual halffield is a function of the right subcortical white matter and the surrounding cortical region at the TPJ. The correct location of primary visual cortex is revealed not until the lesion overlay plot of the patient group with hemianopia is contrasted to an adequate control group. The second row demonstrates the distribution of lesion frequency in 104 patients admitted in the same time period who also had right-sided brain lesions but did not show visual field defects (control group). (B) If the overlay plot of this control group is subtracted from the overlay image of the patient group with hemianopia, the subtraction image now accurately highlights the optic radiation and primary visual cortex. (C) A valid result also is obtained by analyzing
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the same data by voxelwise lesion-behavior mapping (VLBM). VLBM statistically compares the performance of individuals with injury to a voxel to the performance of individuals where that voxel is not injured. Illustrated are all voxels in which a significant difference between the patients with and without hemianopia was revealed (controlled for dependent multiple comparisons using a 1% false discovery rate threshold). (See Color Plate 3.1) (Adapted with permission from Rorden & Karnath, 2004, with permission from Nature Publishing Group, Nature Reviews Neuroscience, 5, 813–819.)
Based on such new analysis techniques, four recent studies compared the location of brain lesions in patients with and without AHP (Baier & Karnath, 2008; Berti et al., 2005; Karnath, Baier, & N€agele, 2005; Vocat & Vuilleumier, Chapter 17, this volume). Karnath and colleagues (2005) investigated 14 consecutively admitted acute stroke patients with right brain damage who showed the false belief that they are not paralyzed. Twelve of these patients showed leftsided plegia and in two patients the left-sided limb(s) were severely paretic. The motor defect thus was homogeneously represented in this group: The majority of the sample (86%) demonstrated complete absence of movement (plegia). Since many of the patients with AHP had additional neurological defects such as spatial neglect, extinction, etc., the control group had to be selected such that all neurological defects were present with the same frequency and severity, except for the critical variable to be investigated: the false belief of not being paralyzed. The authors thus compared the AHP patients with a group of 13 right brain damaged acute stroke patients admitted in the same period who had no AHP but who were comparable with respect to age, acuity of lesion, size of lesion, strength of hemiparesis/-plegia, the frequency of sensory loss, and the frequency of additional spatial neglect, extinction, and visual field defects. Lesion analysis between the groups revealed that the right posterior insula was commonly damaged in patients showing the false belief about the functioning of their own limbs but was significantly less affected in patients without that disorder (see Figure 3.2A). Thus, the authors speculated that the right insular cortex might be a crucial anatomical region in integrating input signals related to self-awareness about the functioning of body parts. A study by Berti and colleagues (2005) also examined 30 patients with rightsided brain lesions and contralateral hemiplegia. The superimposed lesion plots of 17 patients with AHP and neglect were compared to 12 patients with neglect but without AHP. Their findings revealed that AHP was associated with lesions affecting the dorsal premotor cortex (Broadman’s area [BA] 6) and BA 44, motor area BA 4, somatosensory cortex, BA 46, as well as the insula. The authors concluded that, in particular, premotor areas 6 and 44, motor area 4, and the somatosensory cortex are part of a system relevant for motor control as well as self-awareness of motor actions. In our opinion the main difference between their findings and those obtained by Karnath and colleagues (2005) is that Berti et al. (2005) used a very specific selection of subjects for their control group. The control
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THE STUDY OF ANOSOGNOSIA
Figure 3.2 (A) Overlay plot of the subtracted superimposed lesions of a group of right brain damaged patients with anosognosia for hemiparesis/-plegia (AHP) minus a group of patients without AHP (control group). Wh. mat. ¼ white matter. (Adapted from Karnath et al., 2005, with permission from The Society for Neuroscience, The Journal of Neuroscience, 25(31), 7134–7138.) (B) Overlay plot of the subtracted superimposed lesions of a patient group showing a disturbed sense of limb ownership (DSO) and AHP minus a control group without the disorder. (From Baier & Karnath, 2008, with permission from the American Heart Association, Stroke, 39, 486–488.) In each panel, the percentage of overlapping lesions of the anosognosia patients after subtraction of controls is illustrated by five colors coding increasing frequencies from dark red (difference ¼ 1% to 20%) to white-yellow (difference ¼ 81% to 100%). Each color represents 20% increments. The colors from dark blue (difference ¼ –1% to –20%) to light blue (difference ¼ –81% to –100%) indicate regions damaged more frequently in control patients. MNI z-coordinates of each transverse slice are given. In concordance, the two independent patient samples and analyses (A and B) revealed that the right insula is commonly damaged in patients with AHP and DSO but is significantly less affected in patients without these disorders. (See Color Plate 3.2)
subjects, that is, the patients with spatial neglect but without AHP, had mainly lesions of subcortical structures such as the basal ganglia, thalamus, and periventricular white matter (Berti et al., 2005; their Figure 1B). However, more frequently spatial neglect is associated with cortical lesions, involving parietal, temporal, and/ or frontal regions (Buxbaum et al., 2004; Committeri et al., 2007; Heilman, Watson, Valenstein, & Damasio, 1983; Husain & Kennard, 1996; Karnath,
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Ferber, & Himmelbach, 2001; Karnath, Fruhmann Berger, K€ uker, & Rorden, 2004; Vallar & Perani, 1986). A neglect control group, in which the cortical lesion sites associated with spatial neglect are underrepresented, controls only for the subcortical sites of spatial neglect. When such a group is used as a control for a group of patients suffering from both AHP and spatial neglect, the resulting lesion contrast map does not only reveal brain areas related to AHP. In addition, the contrast map shows also those areas that are linked (at the cortical level) with spatial neglect. Part of the cortical brain regions revealed by Berti and colleagues (2005) thus most likely represent neural correlates of spatial neglect rather than of AHP. Evidence supporting the hypothesis that the right insular cortex might be a crucial anatomical region in integrating input signals related to self-awareness about the functioning of body parts (Karnath et al., 2005) has been reported from two further studies investigating lesion localization in AHP. The first study examined a series of 79 acute stroke patients with right brain damage and hemiparesis/-plegia showing AHP versus not showing AHP (Baier & Karnath, 2008). In correspondence with their earlier findings, in this new patient sample the authors found that the brain area more frequently affected in AHP patients compared to controls was the right insular cortex (Figure 3.2B; for details, see subsequent paragraph). The second study analyzed the structural damage of patients with AHP in relation to their anosognosia scores collected 3 days after the stroke and a second assessment 1 week later (Vocat & Vuilleumier, Chapter 17, this volume). In both phases, the authors found the most distinctive lesion areas in the right insular cortex and adjacent anterior subcortical structures. One week post-stroke, additional regions were observed in the right hemisphere. They included the parieto-temporal junction, premotor areas, and the amygdalo-hippocampal complex. The authors interpret these sites as constituents of a network of interacting cerebral regions involved in the occurrence and persistence of AHP.
Disturbed Sense of Ownership The studies of Karnath et al. (2005), Berti et al. (2005), as well as Vocat and Vuilleumier (Chapter 17, this volume) concentrated on the phenomenon of a disturbed feeling of being causally involved in an action—the sense of agency. Whether the patients included in these investigations also experienced their paretic/plegic limb(s) as not belonging to them (i.e., whether they had a DSO) was not reported. A recent study addressed this issue, examining the neural correlate of a DSO (Baier & Karnath, 2008). The authors investigated a series of 78 subjects with acute right hemisphere stroke and left-sided hemiparesis/plegia. They found a ‘‘disturbed sensation of ownership’’ (DSO) for the paretic/ plegic limb(s) in 11 subjects, that is, in 14% of their patient sample. Interestingly, all 11 patients suffered from a false belief of not being paralyzed, that is, also showed a disturbed sense of agency. The brain lesions of these patients were contrasted to those of 11 acute right hemisphere stroke patients
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without such disorder but who were comparable with respect to age, acuity of lesion, size of lesion, strength of hemiparesis/-plegia, and the frequency of additional spatial neglect and visual field defects. Lesion analysis between the groups revealed that the right posterior insula was more frequently affected in patients showing a disturbed experience of own limbs and actions (see Figure 3.2B). The data suggested a tight anatomical relationship between the two phenomena. The authors concluded that the right insula might be involved not only in the genesis of one’s belief about limb movement but also in our sense of limb ownership.
Right Insula for Our Sense of Limb Ownership and Self-Awareness of Actions The Island of Reil, or the insular cortex, is the cortical tissue beneath the frontal and temporal lobe that consists of four to seven oblique gyri encircled by the insular sulcus (Augustine, 1996; Duvernoy, 1999; Mesulam & Mufson, 1985; Naidich et al., 2004; Rhoton, 2007; T€ure, Ya¸sargil, Al-Mefty, & Ya¸sargil, 1999). The central sulcus of the insula divides the insular cortex into a large anterior part and a posterior part (Naidich et al., 2004). The anterior part is divided by several shallow sulci into three to five short gyri, whereas the posterior insular cortex is formed by the anterior and the posterior long gyri. While the anterior part has more extensive connections with limbic, paralimbic, olfactory, gustatory, and autonomic structures, the major projections of the posterior insula include those with the primary and secondary somatosensory area (SI, SII), the superior and inferior temporal areas, parietal cortices, orbitofrontal, prefrontal, and premotor cortex, auditory cortex (AI, AII), amygdala, thalamus, basal ganglia, and the cingulate gyrus (Augustine, 1996; Flynn, Benson, & Ardila, 1999; Mesulam & Mufson, 1985). Converging evidence has been reported that the anterior insular cortex is a central structure for pain mechanisms and temperature regulation (Brooks, Nurmikko, Bimson, Singh, & Roberts, 2002; Craig, Chen, Bandy, & Reiman, 2000; Craig, Reiman, Evans, & Bushnell, 1996; Frot & Maugi`ere, 2003; Kong et al., 2006; Maih€ofner, Kaltenh€auser, Neund€orfer, & Lang, 2002; Schreckenberger et al., 2005). This led to the view that this cortical area might represent an important correlate of human ‘‘interoception’’ (Craig, 2002, 2009). Other interoceptive stimuli that have been shown to be associated with the anterior insula were, for example, taste perception (Faurion, Cerf, Le Bihan, & Pillias, 1998; Ogawa et al., 2005), thirst (Farrell et al., 2006), and autonomic functions such as blood pressure regulation (Kimmerly, O’Leary, Menon, Gati, & Shoemaker, 2005), visceral motor functions (Humbert & Robbins, 2007), and bladder control (Griffiths, Tadic, Schaefer, & Resnick, 2007). Moreover, the anterior insular cortex was suggested to be involved in emotional feelings such as anger or anxiety (Damasio et al., 2000; Ehrsson et al., 2007; Paulus & Stein, 2006; Phillips et al.,
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1997; Stein, Simmons, Feinstein, & Paulus, 2007), in craving (Contreras, Ceric, & Torrealba, 2007; Naqvi, Rudrauf, Damasio, & Bechara, 2007), and in visual selfrecognition (Devue et al., 2007). It has been suggested that the posterior insular cortex might represent a somatosensory association area (Augustine, 1996; Mesulam & Mufson, 1985). Neurons in this area showed responsiveness to auditory and to somatosensory stimulation, the latter with large receptive fields covering the limbs, trunk, or entire body (Schneider, Friedman, & Mishkin, 1993). Several investigators also reported a link between the posterior insula and motor processes. In patients with an insular tumor (Fiol, Leppick, Mireles, & Maxwell, 1988) or an aneurysm lying on the insula (Schneider, Calhoun, & Kooi, 1971), an epileptic aura consisting of rotational and circling limb movements was reported. Early stimulation experiments at the posterior insula reported that gross movements (Showers & Laucer, 1961), as well as restricted movements of single muscles or small groups of muscles, could be elicited (Sugar, Chusid, & French, 1948). However, these latter findings lack confirmation using more recent neurophysiological techniques. Lesion and functional imaging studies in humans further suggested that the posterior insula may be part of the human vestibular system (Bense et al., 2004; Brandt, Dieterich, & Danek, 1994; Dieterich & Brandt, 2008) and might be involved in language and articulation processes in the left hemisphere (Cereda, Ghika, Maeder, & Bogousslavsky, 2002; Dronkers, 1996), as well as in processes of spatial exploration and orientation in the right hemisphere (Karnath et al., 2004). The recent findings (see above) deriving from lesion localization in patients with AHP and DSO suggest that the right insular cortex may also play a crucial role in the genesis of our sense of limb ownership and our self-awareness of limb movement (Baier & Karnath, 2008; Karnath et al., 2005). This hypothesis is supported by other observations. For example, Cereda and colleagues (2002) documented that even a small, isolated lesion of the right insula suffices to induce a DSO for the contralesional limb(s). They screened a total of 4,800 stroke patients from the Lausanne Stroke Registry to identify patients showing a lesion restricted to only the insular cortex. They found four patients and identified five characteristic clinical disturbances of insular strokes: (1) somatosensory deficits with contralateral pseudothalamic sensory stroke in three patients; (2) taste disorder in a patient with a left posterior insular infarct; (3) pseudovestibular syndrome in three patients with posterior insular infarct; (4) cardiac disturbance with hypertensive disorder in one patient with right posterior insular infarct; and (5) neuropsychological disorders, including aphasia (left posterior insular infarct) and—interesting in the present context—one patient with damage to the insular cortex who showed DSO. This latter patient was one of the two patients with a right-sided insular infarct identified by Cereda and colleagues (2002). The 75-year-old right-handed woman was hospitalized after she woke up in the night with a sensation of being touched by a stranger’s hand and alarmed by a foreign body in her bed, not recognizing her own left upper limb.
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Further evidence that the right insula is involved in our feeling of body ownership and our self-awareness of limb movement comes from studies using caloric vestibular stimulation. Positron emission tomography (PET) imaging has revealed that vestibular stimulation induces activation predominantly of the right posterior insula as well as the right temporoparietal junction, SI and SII, retroinsular cortex, putamen, and anterior cingulate cortex (Bottini et al., 1994, 2001; Emri et al., 2003). Therefore, it is interesting that such stimulation in patients with right brain damage may induce transitory remission of AHP and of DSO (Bisiach, Rusconi, & Vallar, 1991; Cappa, Sterzi, Vallar, & Bisiach, 1987; Rode et al., 1992; Vallar, Bottini, & Sterzi, 2003). Spinazzola and colleagues (2008) investigated four right brain damaged patients showing anosognosia for hemianaesthesia. Interestingly, all four subjects presented a lesion including the right insular cortex. This suggests that not only processes linked with AHP but also with anosognosia for hemianaesthesia appear to be associated with the right insula. Supporting evidence for the role of the right posterior insula for self-awareness of limb actions also comes from recent PET experiments (Farrer et al., 2003; Farrer et al., 2004; Tsakiris et al., 2007a). Farrer et al. (2003) found involvement of the right posterior insula when subjects had to indicate whether movements they saw corresponded to their own executed movements or were controlled by someone else. The authors observed a gradually reduced activity of the right posterior insula with an associated gradual decreased feeling of controlling a movement. The level of activity in the right posterior insula correlated with the experience of controlling an action. Right insular activity was high when the subjects experienced a concordant feeling between the viewed and the actually executed movement. Another PET study by the same group showed that in patients with schizophrenia the subjects’ degree of movement control was related to regional cerebral blood flow in the right angular gyrus but not in the insular cortex (Farrer et al., 2004). The authors argued that the differences in activation between normal subjects (Farrer et al., 2003) and patients with schizophrenia (Farrer et al., 2004) might reflect the impaired recognition of one’s own actions in patients with schizophrenia. A recent fMRI study explored the mechanisms of disembodiment (CorradiDell’Acqua et al., 2008). The authors presented a movie in which three fictional players were throwing each other a ball. Each subject’s key-press could either be synchronous or asynchronous with one of the player’s actions. The study revealed that the left posterior insular cortex was activated when the movements of the subjects were synchronous with those of the players in the video game. The finding could suggest that not only the right but also the left insula is involved in mechanisms differentiating between one’s own body and the external environment. An experimental paradigm that allows manipulation of the feeling of body ownership is the rubber hand illusion (Botvinick, 2004; Botvinick & Cohen, 1998). Studies have found that the observation of a rubber hand being stroked
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Figure 3.3 The rubber hand illusion. In the illusion, the subjects observe a facsimile of a human hand (the rubber hand) while their own hand is hidden from view (A). Synchronously touching of the subject’s hand and of the artificial hand with a probe leads to the illusion that the rubber hand belongs to one’s own body (B).
synchronously with one’s own hidden hand can cause the rubber hand to be attributed to one’s own body (see Figure 3.3). This paradigm was applied in a recent PET study (Tsakiris et al., 2007a). Healthy subjects saw either a right or a left rubber hand being touched either synchronously or asynchronously with respect to their own hidden right hand. Across all conditions, participants judged the felt position of their own hand before and after visuotactile stimulation. The proprioceptive judgment was used as a behavioral measure of the phenomenal incorporation of the rubber hand into one’s own body. The authors found that the elicited feeling of ownership for the rubber hand was positively correlated to activity in the right posterior insula and the right frontal operculum. Conversely, when the rubber hand was not attributed to the self, activity was observed in the contralateral parietal cortex, particularly the somatosensory cortex. Tsakiris and colleagues concluded that the posterior insula is active even in the absence of movement and efferent information, that is, when a nonacting subject integrates multisensory information to decide if a body part belongs to one’s own body. Based on this finding they proposed that the posterior insula incorporates the sense of body ownership per se. Craig has argued that the sense of the physiological condition of the body, that is, the ‘‘interoception’’ (see above), which is associated with autonomic control, is engendered in the right anterior insula and might present the basis for our awareness of the ‘‘feeling self’’ (Craig, 2002, 2009). He suggested that this area might represent a polymodal integration zone involved in all human feelings and thus may contain a representation of ‘‘me’’ as a feeling entity, engendering the fundamental phenomenon of human subjective awareness (Craig, Chapter 4, this
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volume). Evidence for this view comes from the various observations that the insula is involved in pain mechanisms, temperature regulation, in subjective feelings such as anger or anxiety, or in autonomic regulation processes (for a more detailed review, see Craig, 2009). Direct evidence that the interoceptive systems implemented in the insular cortex are associated with the sense of body ownership has come from two recent studies using the rubber hand illusion paradigm. Moseley and colleagues (2008) found that the sense of body ownership and the autonomic regulation of the body are tightly linked. They observed that the feeling of ownership for a rubber hand was associated with a decrease of the skin temperature of the real hand. This effect was limb specific, that is, a decrease of skin temperature only occurred in the aligned, hidden real hand. Ehrsson and colleagues (2007) showed that threat to the rubber hand can induce a similar level of activity in the brain areas associated with anxiety and interoceptive awareness, that is, anterior insular and anterior cingulate cortex, as when the person’s real hand is threatened. Their findings thus suggest that incorporated artificial limbs can evoke the same feelings as real limbs. It appears as if indeed our sense of body ownership is tightly linked with the insular interoceptive systems.
Conclusions In the normal experience of an action, the sense of agency and the sense of ownership coincide. Recent findings have suggested that these two feelings are closely linked in brain-damaged patients as well. In stroke patients with AHP, a disturbed feeling of being causally involved in an action often seems to be associated with a disturbed feeling of body ownership. Also, both senses seem to share common neural structures. New lesion mapping and analysis methods revealed that the false belief about the functioning of one’s own limbs, as well as a disturbed sensation of ownership with respect to these limbs, is associated with damage involving particularly the right insula. Functional brain imaging studies supported the role of the right posterior insular cortex in self-awareness of actions and in our sense of limb ownership. Thus, it seems as if the right insula plays a central role for both senses: our sense of limb ownership as well as our sense of agency. The insular cortex is characterized by an extensive spectrum of cortical and subcortical somatosensory and motor connections. The right posterior insula thus may constitute a central node of the network involved in human body scheme representation.
Acknowledgments This work was supported by the Bundesministerium f€ ur Bildung und Forschung (BMBF-Verbundprojekt ‘‘R€aumliche Orientierung’’ 01GW0641) and the
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Deutsche Forschungsgemeinschaft (KA 1258/10–1). We are grateful to Bud Craig, Aikaterini Fotopoulou, George P. Prigatano, and Patrik Vuilleumier for their insightful comments and discussion. We also would like to thank Andrea Klein for Figure 3.3 illustrating the rubber hand illusion as well as Jennifer Gray for her help with the English language. References Anton, G. (1893). Beitr€age zur klinischen Beurtheilung und zur Localisation der Muskelsinnst€orungen im Grosshirne. Zeitschrift f€ ur Heilkunde, 14, 313–348. Appelros, P., Karlsson, G. M., Seiger, A., & Nydevik, I. (2002). Neglect and anosognosia after first-ever stroke: Incidence and relationship to disability. Journal of Rehabilitation Medicine, 34, 215–220. Augustine, J. R. (1996). Circuitry and functional aspects of the insular lobe in primates including humans. Brain Research Reviews, 22, 229–244. Babinski, J. (1914). Contribution a` l’etude des troubles mentaux dans l’hemiplegie organique cerebrale (anosognosie). Revue Neurologique, 27, 845–848. Baier, B., & Karnath, H.-O. (2005). Incidence and diagnosis of anosognosia for hemiparesis. Journal of Neurology, Neurosurgery, and Psychiatry, 76, 358–361. Baier, B., & Karnath, H.-O. (2008). Tight link between our sense of limb ownership and self-awareness of actions. Stroke, 39, 486–488. Bakchine, S., Crassard, I., & Seilhan, D. (1997). Anosognosia for hemiplegia after a brainstem haematoma. A pathological case. Journal of Neurology, Neurosurgery, and Psychiatry, 63, 686–687. Bense, S., Bartenstein, P., Lochmann, M., Schlindwein, P., Brandt, T., & Dieterich, M. (2004). Metabolic changes in vestibular and visual cortices in acute vestibular neuritis. Annals of Neurology, 56, 624–630. Berti, A., Bottini, G., Gandola, M., Pia, L., Smania, N., Stracciari, A., Castiglioni, I., Vallar, G., & Paulesu, E. (2005). Shared cortical anatomy for motor awareness and motor control. Science, 309, 488–491. Berti, A., & Pia, L. (2006). Understanding motor awareness through normal and pathological behavior. Current Directions in Psychological Science, 15, 245–250. Bisiach, E., Rusconi, M. L., & Vallar, G. (1991). Remission of somatoparaphrenic delusion through vestibular stimulation. Neuropsychologia 29, 1029–1031. Bisiach, E., Vallar, G., Perani, D., Papagno, C., & Berti, A. (1986). Unawareness of disease following lesions of the right hemisphere: Anosognosia for hemiplegia and anosognosia for hemianopia. Neuropsychologia, 24, 471–482. Bottini, G., Karnath, H.-O., Vallar, G., Sterzi, R., Frith, C. D., Frackowiak, R. S., & Paulesu, E. (2001). Cerebral representations for egocentric space: Functional-anatomical evidence from caloric vestibular stimulation and neck vibration. Brain, 124, 1182–1196. Bottini, G., Sterzi, R., Paulesu, E., Vallar, G., Cappa, S. F., Erminio, F., Passingham, R. E., Frith, C. D., & Frackowiak, R. S. (1994). Identification of the central vestibular projections in man: A positron emission tomography activation study. Experimental Brain Research, 99, 164–169. Botvinick, M. (2004). Probing the neural basis of body ownership. Science, 305, 782–783. Botvinick, M., & Cohen, J. (1998). Rubber hands ‘‘feel’’ touch that eyes see. Nature, 391, 756.
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4
The Insular Cortex and Subjective Awareness A. D. (Bud) Craig
In the preceding chapter, Karnath and Baier described clinical documentation for a crucial role of the insular cortex in anosognosia for hemiplegia and hemianesthesia, that is, the lack of awareness of feelings of functionally impaired movement or touch in the contralateral body. In this chapter, I present evidence that all feelings from the body are substantialized by an ascending sensory pathway to the posterior insula of primates that represents the physiological condition of the body (Craig, Bushnell, Zhang, & Blomqvist, 1994; Craig, 2002, 2003a). The evidence indicates that integration of this pathway in the mid-insula leads to a polymodal zone in the anterior insular cortex (AIC) of the human brain that is uniquely involved in the subjective perception of feelings from the body (Craig, Chen, Bandy, & Reiman, 2000; Craig, 2002). Further, the AIC is activated in imaging studies of all subjective feelings and emotions in humans, and thus this evidence supports the proposal of the James-Lange theory of emotion (James, 1890) and Damasio’s ‘‘somatic marker’’ hypothesis (Damasio, 1993) that the representation of the sentient self is based on the homeostatic condition of the body. Finally, recent observations from a broad range of imaging and clinical studies provide convergent findings that extend this hypothesis to suggest that the AIC and the adjacent frontal operculum may engender the fundamental phenomenon of subjective human awareness of oneself, others, and all salient perceptions (Craig, 2009). This chapter presents the perspective of a functional neuroanatomist who has studied the neural basis for feelings from the body employing such techniques as single-unit microelectrode recordings, tract-tracing, psychophysics, and functional imaging. First, I will review the functional anatomy of the ascending pathway for feelings from the body. Then I will discuss the integration of such activity with salient environmental, motivational, and social factors, which seems to provide the basis for a coherent representation of all feelings, or the 63
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sentient self, in the AIC. The evidence supporting the concept that the AIC engenders phenomenal awareness will be presented next, followed by the outline of a structural model of awareness that could explain these findings. More detailed presentations of these findings and ideas are available elsewhere (Craig, 2002, 2003a, 2009). This chapter concludes with comments on the relevance of these findings for clinicians studying patients with anosognosia or insular damage.
The Interoceptive Pathway to Insular Cortex for Feelings from the Body Humans perceive feelings from the body that provide a sense of their physical condition and underlie mood and emotional state. In the conventional view presented in most textbooks, the well-discriminated feelings of temperature, itch, and pain are associated with an ‘‘exteroceptive’’ somatosensory system that represents haptic touch and proprioception, whereas the less distinct visceral feelings of vasomotor activity, hunger, thirst, and internal sensations are associated with a separate ‘‘interoceptive’’ system. That categorization, originally espoused by Sherrington (1948), ignores several fundamental discrepancies, such as the fact that lesions or stimulation of the somatosensory cortices rarely affect temperature, itch, or pain sensation, and the fact that all such feelings from the body, in contrast to mechanical touch and proprioception, are endowed with inherent emotional (affective/motivational) qualities and reflexive autonomic effects. The findings I describe here lead to a conceptual shift that resolves these issues by showing that all affective feelings from the body are represented in a novel, unforeseen pathway, phylogenetically unique to primates and welldeveloped in humans, which evolved from the afferent limb of an evolutionarily ancient, hierarchical homeostatic system that maintains the integrity of the body. These feelings thus represent a sense of the physiological condition of the entire body, which I refer to as ‘‘interoception’’ redefined (Craig, 2002).
Spinal and Brainstem Organization The neural processes (autonomic, neuroendocrine, and behavioral) that maintain an optimal physiological balance in the body, collectively called homeostasis, must receive sensory inputs that report the condition of the tissues of the entire body (Cannon, 1939). The small-diameter (A-delta and C) sensory fibers that innervate all tissues of the body (including skin, muscle, joints, teeth, bone, and viscera) and respond selectively to all manner of physiological conditions (including mechanical, thermal, and metabolic changes) provide the necessary homeostatic afferent input. Such sensory fibers in parasympathetic nerves (e.g., vagal and glossopharyngeal) send their central terminals to the nucleus of
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the solitary tract (commonly abbreviated NTS for the Latin name, nucleus tractus solitarius) in the brain stem, and the A-delta and C sensory fibers in somatic and sympathetic nerves send their central terminals to the spinal cord, where they terminate monosynaptically on neurons in lamina I of the superficial dorsal horn. The ontogeny of these fibers is intimately linked with the development of lamina I cells, indicating that together they form a coherent homeostatic afferent system. Thus, lamina I cells do not arise from cells of the dorsal placode, but rather from the progenitors of autonomic interneurons in the lateral horn, and they ascend to the top of the dorsal horn (during a ventromedial rotation of the entire dorsal horn) at precisely the right time to meet the ingrowing smalldiameter fibers from the small dorsal root ganglion (B) cells (Altman & Bayer, 1984). In contrast, the large-diameter fibers, which arise from a distinct set of large dorsal root ganglion (A) cells, grow into the dorsal horn earlier and contact large cells of the dorsal placode that end up at the base of the dorsal horn (because of the rotation) and connect to ventral horn motoneurons. As described below, this ancient structural pattern of organization, that is, an interoceptive (homeostatic) afferent system in the superficial dorsal horn that controls smooth muscle and an exteroceptive system in the base of the dorsal horn that controls skeletal muscle, is maintained in the organization of regions that receive somatic afferent activity in the cerebral cortex of humans. The central projections of lamina I cells confirm the view that they provide the central continuation of the small-diameter afferent system and subserve homeostasis. Lamina I neurons project densely to the spinal autonomic cell columns, thus forming a spino-spinal loop for somato-autonomic reflexes, and they project to the cardiorespiratory integration and preautonomic sites in the brain stem, which likewise receive dense input from the NTS (Craig, 1993, 1995). The concept that lamina I serves as a homeostatic afferent integration site is strikingly corroborated by the observation that lamina I and the autonomic cell columns are the only spinal targets of descending fibers from the hypothalamus (Holstege, 1988). The small-diameter primary afferent fibers selectively signal changes in the physiological condition of the tissues of the body (for references, see Craig, 2003a). For example, one class of C-fibers is sensitive only to itch-producing agents, and another is sensitive only to light (sensual) touch. Accordingly, lamina I neurons comprise several distinct modality-selective classes that receive input from specific subsets of small-diameter primary afferent fibers. The various classes of lamina I cells can be differentiated on the basis of cell shape, afferent responses, electrophysiological properties, axonal projections, descending modulation, and pharmacological properties, and so they can be regarded as virtual ‘‘labeled lines’’ (Craig, 2003a). Their responses correspond very well with the psychophysical characteristics of the several distinct affective feelings from the body that humans perceive, including first (sharp) pain, second (burning) pain, cooling, warm, itch, sensual touch, and muscle burn and cramp.
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In contrast to prior descriptions of lamina I as a ‘‘pain and temperature’’ processing stage, a comprehensive view of the evidence suggests that the distinct types of lamina I neurons provide the substrate for the modality-selective somatoautonomic adjustments that support ongoing homeostasis. For example, innocuous thermoreceptive (cool) activity that is conveyed by thermoreceptive-specific lamina I neurons to the brain stem linearly modulates respiratory parameters, consistent with the primordial role of thermoreception in thermoregulation (Diesel et al., 1990). The lamina I neurons that are directly related to human pain sensation are also essentially homeostatic in nature. In particular, consider the multipolar lamina I cells driven by polymodal nociceptive C-fibers, which uniquely correlate with the feeling of second (burning) pain during specific psychophysical paradigms, such as the repeated brief contact heat test or the thermal grill pain illusion (Craig & Andrew, 2002; Craig & Bushnell, 1994). The accelerating response of these neurons to noxious cold does not begin at the cold temperatures we call noxious ( left) insula, anterior cingulate, dorsomedial frontal lobes, and the ventral orbitofrontal cortex, as well as parts of the basal ganglia (Rosen et al., 2002). The clinical criteria for diagnosing bvFTD rely almost entirely on behavior symptoms, including early decline in interpersonal conduct, early decline in personal conduct, and early emotional blunting (Neary et al., 1998). The SemD subtype of frontotemporal lobar degeneration (FTLD) affects primarily the anterior
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temporal lobes and amygdalae, but it also affects the insula, anterior cingulate, subgenual cingulate/orbitofrontal cortex, and basal ganglia (Rosen et al., 2002). Though the Neary clinical criteria for diagnosing SemD focuses on language symptoms (Neary et al., 1998), SemD patients can show social withdrawal, loss of empathy, impaired judgment, bizarre behavior, denial of illness, and mental rigidity depending largely on their degree of right temporal pathology (Bathgate et al., 2001; Bozeat et al., 2000; Edwards-Lee et al., 1997; Miller, Chang, Mena, Boone, & Lesser, 1993; Perry et al., 2001). The second category includes neurodegenerative diseases for which there is some information available concerning social behavior and personality, but clinical research on the topic is limited to case reports or small studies, and the nature and prevalence of social behavior changes is not well established. In this group are progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), dementia with Lewy bodies (DLB), and progressive nonfluent aphasia (PNFA). Progressive supranuclear palsy is characterized by significant damage to brainstem and subcortical structures (Boxer et al., 2006). Clinically, in addition to atypical parkinsonism, PSP patients have significant cognitive deficits consistent with a frontal-subcortical disconnection syndrome (Litvan, 2002) and may also present with a frontal behavior syndrome that includes loss of insight (O’Keefe et al., 2007) and social disengagement (Litvan, Mega, Cummings, & Fairbanks, 1996). Corticobasal degeneration has many neuropathological similarities to both FTLD and PSP, and it presents with a variety of clinical syndromes affecting frontal and parietal cortex and white matter (Boxer et al., 2006). The aphasic subgroup is more likely to develop severely self-critical behaviors and depression as a result of the disease (Litvan, Cummings, & Mega, 1998), and a subset of CBD patients present with such substantial changes to personality, social behavior, and insight that they are clinically very similar to bvFTD patients (Kertesz, Martinez-Lage, Davidson, & Munoz, 2000; Mathuranath, Xuereb, Bak, & Hodges, 2000). Few formal studies of social behavior in DLB have been performed; however, clinical accounts suggest that some DLB patients experience increased anger and irritability, odd behavior, and other personality changes (McKeith et al., 2005). Similarly, PNFA patients’ behavior is rarely studied, partly due to the difficulty of finding enough true PNFA patients (Gorno-Tempini et al., 2004), but also because anecdotal clinical evidence suggests that these patients have preserved social and emotional functioning (Mesulam, 2007).
2. Social Self-Knowledge in Neurodegenerative Disease When patients with neurodegenerative disease show any alteration in their ability to recognize their level of functioning, it is typically labeled ‘‘loss of insight’’; however, the affected domain of insight varies widely within and between diseases (Evers, Kilander, & Lindau, 2007), and the literature has unfortunately remained fairly imprecise on this topic.
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Hundreds of studies have been performed to characterize loss of insight in AD (see Kaszniak and Edmonds, Chapter 11, this volume); however, these have nearly uniformly focused on awareness of disease and cognitive and functional deficits, rather than insight into alterations of personality and social behavior. A study by Onor, Trevisol, Negro, and Aguglia (2006) investigated behavioral self-monitoring in AD and mild cognitive impairment (MCI) patients by performing semistructured interviews with subjects and their caregiver-informants asking about behavioral symptoms such as hallucinations, unusual verbal and physical behavior, agitation, irritability, mood, emotion perception, and emotional expression. They found that both MCI and AD subjects underestimated their behavioral symptoms, and overestimated their ability to perceive their caregivers’ emotions. Salmon and colleagues (2008) also found that AD subjects underestimated their degree of behavior disturbances, as did a more recent study by Banks and Weintraub (2008), though the specific manner in which they asked subjects to describe their behavior was unspecified, so it is not clear exactly what element of their behavior the patients were rating. In a study performed by our lab (Rankin, Baldwin, Pace-Savitsky, Kramer, & Miller, 2005), AD patients were asked to describe their current personality using a questionnaire yielding information about eight personality traits such as extraversion, warmth, dominance, and arrogance. For six of the eight personality facets, AD patients’ self-estimates (controlling for actual personality change) were no more discrepant from their informants’ estimates than were those of healthy older control subjects. However, AD patients significantly underestimated the degree to which they behaved in a submissive, unassertive manner, and overestimated their level of extraversion, compared to informant reports. Importantly, the AD group’s self-estimates in these discrepant domains were very similar to their caregivers’ retrospective descriptions of how the patients’ personality had appeared before the onset of neurodegenerative disease. This supports the hypothesis that in AD, inaccurate self-knowledge of personality may derive from a failure of online selfmonitoring of recent personality change, resulting in a static self-concept that no longer matches reality as it is observed by others. Loss of insight into behavioral and personality changes has been much more widely examined in bvFTD. It is an early hallmark of the disease and is even a part of the prevailing diagnostic criteria (Neary et al., 1998). There is some clinical overlap between the diagnoses of bvFTD and SemD (Liu et al., 2004) due to the fact that some patients from both categories have right temporal damage and the concomitant clinical symptoms. Thus, the literature on loss of insight in bvFTD sometimes explicitly examines SemD patients, and at other times it is relevant to this right temporal subset of SemD patients even when the group is not explicitly studied. The data on the prevalence of loss of insight in bvFTD varies due to the different assessment methods and constructs measured. However, in an early study operationalizing insight in a manner consistent with the Neary consensus
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criteria, this was found to be one of the earliest and most highly prevalent symptoms of bvFTD, appearing in 59% of patients at presentation and 100% of patients at 2-year follow-up (Mendez & Perryman, 2002). In fact, this was the only core symptom (other than insidious onset and gradual progression) that was present in 100% of bvFTD patients after 2 years. In the same year, Diehl and Kurz (2002) examined neuropsychiatric symptoms in 30 bvFTD patients and found that loss of insight was the most prevalent symptom, occurring in 90% of their sample. Loss of insight in bvFTD has been measured in a variety of different ways, but there is substantial evidence that the majority of bvFTD patients explicitly deny that their social behaviors are problematic and describe themselves in very positive terms, even when this is directly at odds with how others describe them (O’Keefe et al., 2007; Ruby et al., 2007). Eslinger and colleagues (2005) asked bvFTD, SemD, PNFA, and AD patients to rate themselves in the areas of cognition, behavior, emotion and empathy using three questionnaire rating scales. Patients with bvFTD substantially overrated their self-monitoring and empathic perspective-taking, along with cognitive abilities, while SemD patients overrated their self-monitoring, empathic concern, and empathic perspective-taking. Patients with AD overrated their memory but none of their social and personality behaviors, and PNFA patients were not significantly inaccurate on any self-assessments. All of the groups, however, underrated their level of apathy compared to ratings of control subjects. In our study specifically examining self-awareness of personality and personality change (Rankin et al., 2005), bvFTD patients showed a greater magnitude of inaccuracy in more domains of personality than AD patients. Also, they demonstrated significantly worse self-knowledge in the aspects of personality that had changed the most since the onset of their disease (i.e., coldness, introversion, and submissiveness). In an alternative perspective on the issue of inaccurate self-knowledge in bvFTD, Miller et al. (2001) described a subset of bvFTD patients for whom a central symptom was a profound alteration of fundamental aspects of self (e.g., changing one’s political, social, and religious affiliations and values). Patients were aware of these novel personalities and some could articulate their new beliefs and describe their behavioral routines, suggesting perhaps that online self-monitoring was not their primary deficit. All but one of these patients demonstrated disproportionate hypometabolism in the nondominant frontal lobe. The authors suggest that the disease may have caused the longitudinal self-concept to essentially disintegrate, allowing alternatives to gain ascendance. In support of this idea, there is evidence that unlike AD and SemD patients, who show a temporal gradient to their autobiographical memories, bvFTD patients show a uniform impairment of autobiographical memory across all epochs of their lives (Piolino et al., 2003). It is possible that at least some bvFTD patients not only lose the ability to derive information about
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themselves from online self-monitoring, but also lose track of who they were before the onset of their disease, in contrast to AD patients, who seem to return to their initially strong premorbid self-concept when self-monitoring of current behavior breaks down. Qualitatively, some have suggested that what is often called loss of insight in bvFTD may actually be lack of distress over inappropriate behavior (‘‘anosodiaphoria,’’ or lack of concern), rather than a lack of awareness of these new symptoms. Mendez and Shapira (2005) provide the following observations of patient behavior to support this theory: One patient stated, ‘‘I am shallow now . . . this bothers other people but not me.’’ Another patient would go into stores and restaurants and leave without paying for goods and services. She could describe these episodes and the potential consequences, but she was not distressed or concerned about her behavior. Several other patients conveyed the same lack of concern for doing the right thing despite knowing the difference.
However, this same study found that across their patient sample there was a mixed presentation of positron emission tomography (PET) hypometabolism across frontal and temporal lobes, as well as right and left hemispheres. Also, the study did not examine whether patients with this anosodiaphoria differed anatomically from subjects with true loss of self-knowledge. More recently, Evers and colleagues (2007) attempted to better operationalize loss of insight in a group of eight bvFTD patients, some of whom demonstrated predominantly temporal atrophy and substantial naming deficits and may have overlapped diagnostically with SemD. When the authors used unstructured, conversational interviews to examine patients’ insight into their cognition, personality, functional status, and disease status, three of these patients had preserved insight. However, two of these three had temporal > frontal hypometabolism on a PET scan. While some anatomic studies have correlated loss of insight with frontal damage (Harwood et al., 2005; McMurtray et al., 2006; Mendez & Shapira, 2005), others have found it to correlate with either left or right temporal damage (Ruby et al., 2007; Thompson, Patterson, & Hodges, 2003). These qualitative differences in degree and quality of insight across bvFTD patients suggest that additional clarification is needed, most likely through combining a more fine-grained approach to measuring insight with more careful characterization of anatomic-behavioral correlates using both bvFTD and SemD patients. Thus far, only one quantitative study of insight in CBD and PSP patients has been published, and it found that though their self-awareness of personality change was not as dramatically impaired as that of a comparison group of bvFTD patients, CBD and PSP patients did demonstrate poor insight into their behavioral characteristics (O’Keefe et al., 2007). One other study directly compared accuracy of self-knowledge in VascD patients against that of bvFTD
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patients and found that though the deficits in the VascD group were less severe, they did worsen over the course of the disease (Moretti et al., 2005). Unfortunately, no studies have yet been performed to address accuracy of social self-knowledge in DLB.
3. Social Self-Monitoring in Neurodegenerative Disease If self-knowledge is derived from all of the different sources described in the first section of this chapter (e.g., interoception, exteroception, semantic selfknowledge, implicit and explicit social feedback), this suggests that different types of self-monitoring may be required to derive each particular type of selfknowledge. Thus, focal neurodegenerative conditions would be expected to have a differential impact on social self-monitoring depending on the affected anatomic circuits, resulting in the failure to update self-knowledge in divergent domains. However, careful examination of the process by which patients with neurodegenerative disease lose their ability to self-monitor their social persona is almost entirely missing from the current clinical literature, which thus far has been primarily limited to studying patients’ loss of self-knowledge. In one relevant study, Banks and Weintraub (2008) asked AD, FTD, and PNFA patients to rate their ‘‘behavior’’ (though the authors never specify what questions were asked) before, and then after filling out the Frontal Behavioral Inventory (FBI) questionnaire describing themselves. Patients’ self-ratings after being primed to think about themselves by completing the FBI did not differ significantly from their pre-FBI estimates, suggesting their self-knowledge of behavior did not change. More significantly, all three patient groups’ post-evaluation self-ratings of behavior (i.e., their ‘‘self-monitoring’’) was more inaccurate for behavior than for eyesight or naming ability. The near absence of examination of self-monitoring in neurodegenerative disease is particularly problematic, because loss of social self-monitoring can provide a fascinating window into the sources of behavioral self-regulation in a way that loss of cognitive self-monitoring cannot. When an AD patient demonstrates poor awareness of his or her memory deficits, it is logical to assume that the particular patterns of neural damage leading to the loss of insight are either separate from, or at least partly a result of, the memory loss. However, when an FTD patient demonstrates poor awareness of his or her behavior deficits, we cannot assume that the loss of insight and the social behavior changes are separate processes, or that the loss of insight is merely another symptom of the neural breakdown responsible for his or her inappropriate social behavior. In fact, theoretical models of social behavior suggest that self-monitoring may actually be required for normal social selfcontrol (Eslinger et al., 2005; Miller et al., 2001). This implies that loss of insight may actually temporally precede and even play a causal role in patients’ development of social dysdecorum.
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Novel Studies of Social Self-Monitoring in Neurodegenerative Disease Because of this substantial gap in the literature, we performed some experiments using different approaches to directly assess self-monitoring in neurodegenerative disease patients. Experiment 1 was a pilot study to determine whether the established method of assessing self-monitoring via post-test performance ratings could also effectively be applied to tests measuring social sensitivity. In Experiment 2, we obtained informant ratings of patients’ social self-monitoring, and examined not only the differences across dementia groups but also investigated whether a causal relationship between disinhibited social behavior and loss of social insight could be inferred based on the timing of symptom onset.
Experiment 1 For this experiment, we piloted the use of the standard pre- and post-test selfrating paradigm, not with standard neuropsychological tests or behavior questionnaires, but with direct tests of social and emotional sensitivity. The goal was to elicit divergent patterns of self-ratings over time in different subject groups based on the accuracy and flexibility of their social self-concept when provided an opportunity for online monitoring of test performance. Methods Testing was performed on 39 subjects who included 11 bvFTDs, 3 SemDs (Neary et al., 1998), 9 AD patients (McKhann et al., 1984), 7 CBDs (diagnosed according to the criteria described in Boxer et al., 2006), 3 PSPs (Litvan et al., 2003), and 6 healthy older control subjects (NC) who had a normal neurologic exam and cognitive testing. Subjects were 20 men and 19 women, with an average age of 61.8 years (SD ¼ 8.0), and an average education level of 15.5 years (SD ¼ 3.0). No significant between-group differences were found for sex, age, or education. At the beginning of the testing session, subjects were oriented to a graphic depicting a group of people organized across a normal curve and were taught how to point to the graphic to indicate where they believe they would rank on a skill in relation to ‘‘other people.’’ The subjects’ self-rankings were converted into percentile scores for analysis. They were asked to rank their ability on three occasions for each of the two tests: a pre-test rating (PRE) to estimate the accuracy of their predictive self-knowledge, a post-test rating (POST) to determine the degree to which they exhibited online self-monitoring of their performance, and a third rating at the very end of the test session (END) to determine if any new self-knowledge gained by observing their own performance on the tests was maintained after a delay interval. For each assessment, subjects were asked
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to rank their ability to (1) recognize what emotion someone was feeling by watching a video of that person, and (2) recognize when someone was speaking sarcastically. The tests of social and emotional perception were from The Awareness of Social Inference Test (TASIT; McDonald, Flanagan, Rollins, & Kinch, 2003). For the Emotion Evaluation Test (EET) subtest, subjects watched brief (20-second) videos of actors performing semantically neutral scripts portraying one of the seven basic emotions (happy, surprised, neutral, sad, anxious, frightened, revolted) and were asked to choose the correct emotion from a card on which the seven options are written. To reduce the effects of fatigue on our elderly, demented subjects, we administered only items 1–14, for a maximum score of 14. Subjects also performed the Social Inference-Minimal (SI-M) subtest, for which they watched 30- to 45-second videos of actors expressing themselves in either a sincere or a sarcastic manner, again with semantically neutral, interchangeable scripts (e.g., ‘‘I’d be happy to do it. I’ve got plenty of time.’’) and were asked to answer four yes-no questions about the emotions and intent of the characters. The total score for this test was the sum of correct responses to questions about the two kinds of sarcastic items. Subjects’ actual performance on these tests (ACTUAL) was standardized into percentile scores based on the performance of 22 healthy older controls who did not participate in this self-rating experiment. Results Subjects’ results were analyzed using a mixed regression model (SAS: PROC MIXED), controlling for sex and age, to derive within-group and between-group comparisons across time. Values for PRE, ACTUAL, POST, and END percentile ranks across the six subject groups can be found in Table 14.1 and Figure 14.1. Evidence from studies employing self-ratings of cognitive performance have shown that even normal subjects give widely variable, and often inaccurate, predictive ratings of how they will perform on a test, ostensibly because they do not have a clear idea of the task itself (Eslinger et al., 2005). Thus, we expected predictive ratings to differ from actual performance in all subject groups, including controls. For the emotion evaluation task, PRE ratings were significantly higher than ACTUAL scores in AD, CBD, bvFTD, NC, and SemD groups, but not in the PSP group. For the sarcasm detection task, PRE ratings were significantly higher than ACTUAL scores in the CBD, bvFTD, and SemD groups, but the predictions of the AD, NC, and PSP groups were not significantly higher than their actual scores. The PSP group’s average prediction exactly matched their actual performance, both at the 49th percentile. We hypothesized that after performing the emotion recognition and sarcasm recognition tasks, subjects with intact self-monitoring (e.g., NC subjects) would be able to give a more accurate estimate of their abilities in which their
Table 14.1 Differences across Subject Groups in Self-Ratings of Performance on Tests of Emotional and Social Sensitivity Percentile (SD)
Prediction
Postdiction
End of Session
Actual Score
72.5 (12.9) 62.3 (19.0) 66.7 (28.9) 59.8 (13.6) 67.8 (18.0) 54.7 (7.4)
75.8 (13.9) 61.8 (20.4) 45.3 (37.2) 63.6 (17.3) 72.5 (19.4) 70.0 (18.0)
29.3 (39.1) 12.3 (17.7) 1.3 (0.6) 15.3 (21.1) 22.7 (29.7) 43.3 (32.3)
TASIT: Emotion Evaluation Test NC (n ¼ 6) bvFTD (n ¼ 11) SemD (n ¼ 3) AD (n ¼ 9) CBD/PNFA (n ¼ 7) PSP (n ¼ 3)
67.2 (17.6) 64.1 (23.1) 60.0 (17.3) 57.8 (23.1) 65.1 (16.7) 55.7 (12.4)
Prediction
Postdiction
End of Session
Actual Score
72.8 (13.0) 60.2 (19.1) 65.0 (21.2) 59.3 (12.9) 78.7 (11.8) 60.3 (12.7)
47.3 (30.0) 17.9 (23.4) 6.3 (9.2) 34.4 (25.3) 36.4 (23.0) 49.3 (14.7)
TASIT: Sarcasm Task (SI-M) 61.8 (11.2) 55.3 (18.2) 65.0 (21.2) 53.1 (21.0) 63.6 (24.4) 48.7 (4.0)
65.8 (17.4) 60.1 (21.2) 44.7 (38.3) 60.1 (17.9) 63.0 (26.3) 58.0 (10.8)
AD, Alzheimer’s disease; bvFTD, behavioral variant of frontotemporal dementia; CBD/PNFA, corticobasal degeneration/progressive nonfluent aphasia; NC, normal control subjects; PSP, progressive supranuclear palsy; SemD, semantic dementia.
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Percentile
TASIT Emotion Evaluation Test 100 90 80 70 60 50 40 30 20 10 0 Prediction
NC
FTD
Actual
SemD
Postdiction
AD
End of Session
CBD/PNFA
PSP
Percentile
TASIT Simple Sarcasm Test 100 90 80 70 60 50 40 30 20 10 0 Prediction NC
FTD
Actual SemD
Postdiction AD
CBD/PNFA
End of Session PSP
Figure 14.1 Graph of self-rating performance across diagnostic groups. AD, Alzheimer’s disease; CBD/PNFA, corticobasal degeneration/progressive nonfluent aphasia; FTD, frontotemporal dementia; NC, normal control subjects; PSP, progressive supranuclear palsy; SemD, semantic dementia; TASIT, the awareness of social inference test (Mac Donald, 2003).
POST rating would be closer to their actual score (ACTUAL) than their PRE rating. Conversely, subjects with self-monitoring deficits (e.g., bvFTD patients) would not have adjusted their self-ratings to be closer to their actual performance, and instead would provide a POST rating very similar to their PRE rating. For the emotion
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evaluation task, however, no group showed any change from the PRE estimate to the POST estimate, and every group but the PSP subjects showed significantly higher POST estimates compared to their ACTUAL scores. On the sarcasm detection task, the same pattern was seen, with no significant differences between the PRE and POST estimates in any group, including controls. We also hypothesized that for some subject groups with otherwise intact behavioral self-monitoring, some subjects would forget their actual performance by the end of the evaluation period (e.g., AD patients), in which case their END ratings would be more similar to their PRE ratings than their ACTUAL or POST ratings. Conversely, subjects capable of maintaining and incorporating the new information about their performance into their self-concept (e.g., NC subjects) would provide END ratings that were closer to their POST ratings than their PRE ratings, demonstrating that they had adjusted their self-knowledge to be more accurate based on their experience performing the tests. Contrary to our expectations, no group revised their self-estimate as of their POST assessment; thus, differences between POST and END ratings were not a meaningful way to see whether any revision of self-estimate was maintained over time. On the emotion evaluation task, no subject group showed significant differences between their POST and END ratings, with the exception of the SemD group, who rated themselves as significantly worse at END ratings than their POST ratings. No group showed a significant difference between POST and END ratings of their performance on the sarcasm detection task. Experiment 1 Summary We expected to see divergent patterns across groups of neurodegenerative disease patients as they rated their performances before and after a series of social and emotional awareness tasks. However, with the exception of a very small group of PSP patients (n ¼ 3) on which few generalizations can be based, all subject groups including healthy older controls overestimated their ability to judge emotions and detect sarcasm, both before performing the corresponding tasks and immediately afterward. These data suggest that none of the groups demonstrated online selfmonitoring of their ability to read social signals in response to these social sensitivity tasks, and all groups maintained an inaccurately inflated self-concept of their abilities despite implicit evidence to the contrary.
Experiment 2 Our attempt to obtain direct evidence of self-monitoring of social skills in a faceto-face testing paradigm was largely unsuccessful. However, we also attempted to obtain information on social self-monitoring in a somewhat more ecologically valid manner, by directly asking subjects and a first-degree relative informant about how well the subject recognized and used social feedback from others to alter their behavior.
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Methods For this study, a much larger group of subjects was enrolled (total n ¼ 155: 35 bvFTD, 23 SemD, 42 AD, 14 CBD, 12 PSP, 9 primary progressive nonfluent aphasia [PNFA; Neary et al., 1998], and 20 NC subjects). Subjects included 78 males and 77 females (mean age 62.7 – 7.8; mean education 16.2 – 2.7). Among the nonnormal subjects, mean MMSE ¼ 22.9 – 6.1, mean CDR ¼ 0.9 – 0.5 (i.e., mild dementia). Social self-monitoring behavior was assessed with the Revised SelfMonitoring Scale (RSMS; Lennox & Wolfe, 1984), a 13-item questionnaire that is a revision of the original Snyder Self-Monitoring Scale (Snyder, 1974). The first subscale, ‘‘Sensitivity to the expressive behavior of others,’’ (RSMS-EX) is designed to assess awareness of subtle emotional and social cues specifically concerning one’s own behavior (e.g., ‘‘I can usually tell I’ve said something inappropriate by reading it in the listener’s eyes.’’). The second subscale, ‘‘Ability to modify self-presentation’’ (RSMS-SP), measures the ability to respond to social context and interpersonal signals and modify one’s behavior to be more appropriate to the particular needs of the situation. Spouses, relatives, or close friends were asked to fill out the RSMS questionnaire describing the subject’s current characteristics. An informant report on the subject was considered to be a valid estimate of their daily social self-monitoring, because behaviors described by the RSMS all are observable, not only by the subject, but also by people who frequently interact with them. Though we expected some subjects groups to give divergent accounts of their self-monitoring on the RSMS compared to their informants, we still obtained RSMS self-reports from a subset of 123 subjects (NC ¼ 20; bvFTD ¼ 30; SemD ¼ 14; PNFA ¼ 8; AD ¼ 30; CBD ¼ 10; PSP ¼ 11). This subset was biased toward inclusion of patients with fewer cognitive and language deficits who retained the capacity to fill out the questionnaires themselves, while informants were able to report on subjects with more severe cognitive deficits. Informants also provided a report on the subjects’ real-life social behaviors via the Neuropsychiatric Inventory (NPI) structured interview. The NPI Disinhibition subscale total score is a composite of the frequency and severity of socially inappropriate behaviors such as saying crude or hurtful things, touching or speaking to strangers inappropriately, inappropriately disclosing personal information, and acting or speaking impulsively. Results Subjects’ results were analyzed using a general linear model (SAS: PROC GLM), and sex, age, and MMSE were used as covariates in all analyses. bvFTD and SemD subjects were rated on both RSMS-EX and RSMS-SP scores as significantly lower than NC subjects, and no other groups were seen by their informants as having poorer social self-monitoring (Table 14.2).
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Table 14.2 Differences across Subject Groups in Demographics and Scores on the Revised Self-Monitoring Scale (RSMS; Lennox, 1984), including Self-Ratings and Informant Ratings M (SD) Age Sex (M/F) Education CDR
NC (n ¼ 20)
bvFTD (n ¼ 35)
SemD (n ¼ 23)
PNFA (n ¼ 9)
AD (n ¼ 42)
CBD (n ¼ 14)
PSP (n ¼ 12)
61.2 (10.2) (10/10) 17.7 (2.1) 0.05 (0.16)
61.8 (7.0) (27/8) 16.5 (2.2) 1.1 (0.5)
63.5 (5.8) (12/11) 16.2 (2.6) 0.9 (0.5)
66.0 (8.9) (1/8) 15.6 (3.4) 0.5 (0.4)
61.3 (8.2) (22/20) 16.0 (3.1) 0.8 (0.3)
65.1 (6.9) (2/12) 14.3 (1.7) 0.6 (0.5)
66.3 (5.4) (4/8) 15.9 (3.0) 1.0 (0.5)
26.1 (3.9) 26.8 (2.6)
23.8 (6.0) 23.5 (5.9)
21.9 (7.6) 27.7 (4.5)
22.0 (8.4) 24.3 (7.8)*
28.0 (3.7) 26.4 (5.5)
26.4 (3.7) 26.6 (4.7)
24.4 (5.2) 27.5 (6.3)
24.4 (6.2) 22.2 (7.0)
RSMS-EX (Sensitivity to Expressive Feedback) Informant Subject
25.2 (4.7) 26.4 (4.5)
14.0 (5.8)* 24.8 (6.6)
15.7 (7.0)* 21.4 (5.2)
RSMS-SP (Ability to Modify Self-Presentation) Informant Subject
27.8 (2.9) 27.3 (2.5)
19.5 (4.3)* 28.3 (6.1)
20.6 (4.7)* 26.2 (3.9)
* Differs from NC group at p < .05 (Dunnett-Hsu post-hoc test controlling for sex and MMSE). AD, Alzheimer’s disease; bvFTD, behavioral variant of frontotemporal dementia; CBD, corticobasal degeneration; CDR, clinical dementia rating; NC, normal control subjects: PNFA, progressive nonfluent aphasia; PSP, progressive supranuclear palsy; SemD, semantic dementia.
However, when self-reports were examined, no group rated themselves as significantly worse than controls at sensitivity to other’s expressive feedback (RSMS-EX), though SemD subjects showed a nonsignificant trend (p ¼ .072). However, PSP subjects rated themselves significantly lower than controls on their ability to modify their own self-presentation as a result of social feedback (RSMS-SP). When self-informant difference scores were analyzed, the only group whose self-reports were significantly different from that of their informants was the bvFTD group. Based on current models of metacognition (Eslinger et al., 2005), we hypothesized that deficits in behavioral self-monitoring would causally precede deficits in behavioral self-control. We examined the temporal relationship between social self-monitoring and self-control in social situations by analyzing informant reports of the RSMS in relation to NPI Disinhibition scores. These analyses were conducted in two parts. First, regressions were performed, controlling for sex, mini-mental state exam (MMSE), and diagnostic group, to determine if RSMS could significantly predict NPI Disinhibition scores. Both RSMS-EX and
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RSMS-SP showed unique ability to predict Disinhibition (p < .0001). The standardized regression coefficients for both models were of similar magnitude (RSMS-EX beta ¼ 0.28; RSMS-SP beta ¼ 0.34), in models accounting for 47% and 44% of Disinhibition variance, respectively. When RSMS-EX and RSMS-SP are included in the same model, only RSMS-EX demonstrated a unique ability to predict Disinhibition, and RSMS-SP dropped out of the model. However, RSMS-EX and RSMS-SP were significantly correlated, controlling for sex and MMSE, at r ¼ 0.78, suggesting that they have substantial collinearity in a regression analysis, and their relative independent relationships to Disinhibition could not be clearly delineated. Next, to investigate the temporal relationship between loss of social selfmonitoring and loss of social self-control, we performed crosstabs to examine the frequency with which patients showed independent versus comorbid impairments on the RSMS and NPI Disinhibition scales. Continuous scores on these scales were converted to binary ‘‘yes-no’’ values based on whether subjects showed clinically abnormal scores relative to controls. RSMS raw scores for patients (n ¼ 128) were standardized using data from the older normal controls. Subjects obtaining RSMS subscale scores falling below z ¼ 1.30 (i.e. less than 9th percentile, or borderline impaired) were considered to have deficits in selfmonitoring. Subjects with NPI-Disinhibition scores equal to or greater than 5 were considered to have clinically significant disinhibition. Thirty-seven percent of patients were not impaired in either self-monitoring or behavior. Patients who demonstrated deficits in sensitivity to social feedback (impaired RSMS-EX) were about as likely to be disinhibited (NPI-Disinhibition ‘‘yes’’: 25% of subjects) as to not be disinhibited (NPI-Disinhibition ¼ ‘‘no’’: 34% of subjects). However, only 4% of subjects demonstrated no feedback sensitivity deficits (no impairment on RSMS-EX) but were considered disinhibited (NPIDisinhibition ¼ ‘‘yes’’). This suggests that while it is common for patients to have problems monitoring social feedback without concurrent deficits in social selfcontrol, it is very rare for socially disinhibited subjects not to have self-monitoring deficits. This same pattern was true in the RSMS-SP data, where patients were about evenly distributed across the combinations of RSMS-SP and Disinhibition symptoms, but only 5% of patients who were socially disinhibited were seen as having normal sensitivity to social feedback. When the analysis was limited to bvFTD patients, only 3% of socially disinhibited patients had normal RSMS-EX scores, and 5% had normal RSMS-SP scores. Experiment 2 Summary This experiment demonstrated that (1) bvFTD and SemD subjects are poorer at social self-monitoring than healthy older controls and other dementia control groups, (2) bvFTD patients have an explicitly inflated concept of their own ability to monitor social feedback from others, and (3) when social self-
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monitoring data are analyzed alongside of data on loss of social control, very few patients who behave in a socially inappropriate manner do not also have diminished social self-monitoring, while the converse is not true.
Discussion and Conclusions Social Self-Monitoring: Normally Deficient? It was particularly striking that in the very small sample represented in Experiment 1, our healthy normal control subjects overestimated their abilities and were impervious to performance-based feedback, demonstrating a pattern of poor self-monitoring similar to that of patients. Though one other study has employed a similar self-rating of behavior paradigm to assess self-monitoring, they did not ask control subjects to perform this element of the protocol (Banks & Weintraub, 2008). One of the difficulties employing self-ratings of performance with cognitive, rather than social, tasks is that many of the cognitive tasks show ceiling effects in healthy normal patients; thus, their predicted abilities and actual abilities match, and no updating of self-concept is required, or observed. However, when compared to a larger group of well-characterized, healthy older control subjects, two-thirds of control subjects in this study failed the emotion naming task, though all but one of them performed in the average range on the sarcasm detection task. The diverse and even impaired performance observed in the control group would suggest that ceiling effects were not an issue here, and that a subset of the control subjects should have had ample implicit evidence that they were having difficulty with the task, and thus should have revised their selfrating between PRE and POST assessment. It is possible that deficits in social sensitivity cosegregate with deficits in self-monitoring of social skills, so the fact that our small sample of normal controls performed decidedly abnormally on the emotion evaluation task may have been causally related to their abnormally flat self-ratings on the self-monitoring task. It remains to be seen whether a different pattern would occur in a larger group of normal control subjects. However, these results serve to highlight the fact that it is typical for selfappraisals to be positively biased (Robins & Beer, 2001; Taylor & Brown, 1988). It also shows that self-monitoring of performance on social and emotional sensitivity tasks is difficult, perhaps more difficult than self-monitoring of performance on cognitive tasks, since NC subjects are substantially more accurate monitoring their cognition (Eslinger et al., 2005). The results of Experiment 1 also suggest that procedural alterations to the study method might be necessary to provide useful data with regard to selfmonitoring of social and emotional functioning. Consistent with many studies employing the pre- and post-test rating methods for assessment of cognitive deficits (Banks & Weintraub, 2008; Eslinger et al., 2005; O’Keefe et al., 2007) we did not provide subjects with explicit feedback describing their performance
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on these emotion naming and sarcasm detection tasks. The implicit feedback subjects derived from their performance on the task may not have been adequate to cause them to alter their self-concept, perhaps because they did not realize that they were providing incorrect responses. In the future, a paradigm in which subjects are given explicit feedback about their performance (e.g., ‘‘You got four of those wrong.’’) before they are asked for their post-test ratings might yield the evidence of social self-monitoring and revisions of self-assessments that this experiment did not.
Self-Monitoring, Self-Control, and Anatomy: Complex Interrelationships Both experiments provided rudimentary but intriguing evidence that the patterns of social self-monitoring may significantly diverge across dementias, particularly in the form of at least partly preserved self-monitoring in SemD and perhaps even PSP. While SemD patients have some anterior cingulate and orbitofrontal damage, the disease neuroanatomy typically leaves the rest of the frontal lobes intact, making them an excellent control group for bvFTD and AD subjects who typically have more widespread frontal involvement and show more self-monitoring deficits (Banks & Weintraub, 2008). Though AD, bvFTD, and SemD patients can all have deficits in social signal detection (Lavenu & Pasquier, 2005; Rosen et al., 2004), this does not seem adequate to explain the different patterns and degrees of altered self-monitoring across the groups. Additional processes are likely at work, such as altered awareness of interoceptive information and autobiographical self-awareness in bvFTD, or memory loss for exteroceptive behavioral observations in AD. Research is needed that will carefully characterize each of these elements of clinical phenomenology with respect to disease and anatomy. While it is impossible to use this kind of cross-sectional, observational data to definitively establish a temporal sequence of onset between the two symptoms of decreased social self-monitoring and decreased social self-control, the data from Experiment 2 do suggest that loss of social self-control seldom, if ever, occurs outside of the context of loss of self-monitoring. This temporal relationship has already been suggested by cross-sectional symptom prevalence studies that demonstrate that impaired insight affects more bvFTD patients at initial visit than any other symptom, and that it is impaired in 100% of subjects a few years into the disease, whereas other symptoms do not affect all patients (Diehl & Kurz, 2002; Mendez & Perryman, 2002). A causal relationship makes intuitive, logical sense and has previously been suggested by various researchers (Eslinger et al., 2005; Miller et al., 2001). However, currently even specialists in bvFTD approach behavior change and loss of insight as if they are symptoms that are equally likely to occur first, and which are perhaps due to a common pathogenesis, rather than having any discernable temporal or causal relationship.
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Certainly, more carefully designed analysis of the relationship between insight and social behavior is warranted, including longitudinal studies, and studies using more precise measures that discriminate among symptoms of altered self-knowledge, loss of online social self-monitoring, anosodiaphoria, and anosognosia for personality and social behavior. Evidence is multiplying that different diseases involving distinct neurological circuits cause very different patterns of metacognition and social behavior, and more attention must be focused on the diversity of processes underlying the derivation of social self-knowledge. References Addis, D. R., & Tippett, L. J. (2004). Memory of myself: Autobiographical memory and identity in Alzheimer’s disease. Memory, 12, 56–74. Aharon-Peretz, J., Daskovski, E., Mashiach, T., Kliot, D., & Tomer, R. (2003). Progression of dementia associated with lacunar infarctions. Dementia and Geriatric Cognitive Disorders, 16(2), 71–77. Allison, T., Puce, A., & McCarthy, G. (2000). Social perception from visual cues: Role of the STS region. Trends in Cognitive Sciences, 4(7), 267–278. Banks, S., & Weintraub, S. (2008). Self-awareness and self-monitoring of cognitive and behavioral deficits in behavioral variant frontotemporal dementia, primary progressive aphasia and probable Alzheimer’s disease. Brain and Cognition, 67 (1), 58–68. Bathgate, D., Snowden, J. S., Varma, A., Blackshaw, A., & Neary, D. (2001). Behaviour in frontotemporal dementia, Alzheimer’s disease and vascular dementia. Acta Neurologica Scandinavica, 103(6), 367–378. Boxer, A. L., Geschwind, M. D., Belfor, N., Gorno-Tempini, M. L., Schauer, G. F., Miller, B., et al. (2006). Patterns of brain atrophy differentiate corticobasal degeneration from progressive supranuclear palsy. Archives of Neurology, 63, 81–86 . Bozeat, S., Gregory, C. A., Ralph, M. A., & Hodges, J. R. (2000). Which neuropsychiatric and behavioural features distinguish frontal and temporal variants of frontotemporal dementia from Alzheimer’s disease? Journal of Neurology, Neurosurgery, and Psychiatry, 69(2), 178–186. Chatterjee, A., Strauss, M., Smyth, K. A., & Whitehouse, P. J. (1992). Personality changes in Alzheimer’s disease. Archives of Neurology, 49, 486–491. Chen, J. C., Borson, S., & Scanlan, J. M. (2000). Stage-specific prevalence of behavioral symptoms in Alzheimer’s disease in a multi-ethnic community sample. American Journal of Geriatric Psychiatry, 8(2), 123–133. Craig, A. D. (2003). Interoception: The sense of the physiological condition of the body. Current Opinion in Neurobiology, 13(4), 500–505. Critchley, H. D., Wiens, S., Rotshtein, P., Ohman, A., & Dolan, R. J. (2004). Neural systems supporting interoceptive awareness. Nature Neuroscience, 7(2), 189–195. Cummings, J. L. (1997). The Neuropsychiatric Inventory: Assessing psychopathology in dementia patients. Neurology, 48(5 Suppl 6), S10–16.
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15
Anosognosia and Error Processing in Various Clinical Disorders Ian H. Robertson
Do I tend to talk too loudly? Would people consider me brash and insensitive? Am I fat? Am I clever? Am I forgetful? Would others consider me bad tempered? Am I nervous? Much of modern psychology is based on asking individuals to self-evaluate in response to questions such as these, and the results obtained by such self-ratings are often replicable and predictive of real-life behavior tendencies (Manly, Robertson, Galloway, & Hawkins, 1999), as well as differential brain function (Fischer, Wik, & Fredrikson, 1997; Haas, Constable, & Canli, 2008). How, in the m^elee of everyday life, do we manage to observe ourselves sufficiently consistently as to come up with fairly reliable and at least partially valid quantitative and comparative ratings of our behaviors in a bewildering number of dimensions? One prerequisite for this must be adequate attention to key episodes and features of everyday behavior and the second some kind of memorial ‘‘running average’’ of these in the form of summary self-evaluations across a range of dimensions. While there must be some degree of accuracy in self-evaluations in order to produce the replicable relationships that we observe, it is clear that the above attention-memory model cannot be the whole story. Under a number of circumstances, individuals can be inaccurate in their self-evaluations—for instance, underestimation of personal competence in depression (Voelz, Walker, Pettit, Joiner Jr., & Wagner, 2003), overestimation in mania (Leahy, 2005), overestimation of ‘‘fatness’’ in anorexia nervosa (Sachdev, Mondraty, Wen, & Gulliford, 2008), and underestimation of driving competence under the influence of alcohol (Barkley, Murphy, O’Connell, Anderson, & Connor, 2006). Self-evaluation can be inaccurate, and following damage to the brain, this inaccuracy can extend to the extremes of anosognosia across virtually all the 321
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syndromes of disordered brain function outlined in the other chapters of this book. What is clear from these chapters is the many different ways in which awareness of a disability can break down, and the many different cognitive and brain processes that can contribute to the anosognosia. While recognizing the range and complexity of the ways in which self-awareness can break down, the purpose of this chapter is to review evidence for a central role of certain attentional and error-processing mechanisms that may be a common underpinning of many different types of disorders of self-evaluation.
Offline Self-Referential Thought versus Online Self-Evaluation When people are asked to make judgments pertaining to their internal, emotional, or ‘‘self’’ states, medial prefrontal cortex activations (Johnson et al., 2002), and in particular dorsal medial prefrontal activations (Gusnard, Akbudak, Shulman, & Raichle, 2001) are commonly found. During attentionally demanding tasks requiring an external focus, these regions are typically inhibited and dorsolateral prefrontal areas show activations (Manly et al., 2003). Such an ‘‘internal’’ focus—reflecting on the qualities of self and its attributes—may be conceptually separate from the processes involved in evaluating one’s performance in various behavioral dimensions in the course of everyday life. The ‘‘offline’’ judgment as to whether I am, for example, a habitually careless person may depend on quite different cognitive processes from the ‘‘online’’ assessment, in the course of attentionally demanding activities, as to whether in this instance I have been careless. Is there any evidence to support such an assertion? One major source of information about our moment-to-moment performance that contributes to self-evaluation is error. It is when we realize that we have closed the door with the key inside that we recognize our carelessness. The most careless among us may not realize the error until we arrive back home late at night and cannot get into our house. This is an everyday example of what could be referred to as a problem with vigilant attention. My colleagues Hester and Garavan have shown that awareness of error is associated with dorsolateral prefrontal cortex functioning (Hester, Foxe, Molholm, Shpaner, & Garavan, 2005), supporting the view that online evaluation of personal performance draws on different dorsolateral cortical systems than offline self-referential thought. In this chapter, I will expand on this hypothesis, proposing that accurate self-evaluation depends on adequate levels of vigilant attention, and that intact error-processing mechanisms are a key contributor to this attention and, by implication, to self-evaluation.
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Vigilant Attention Vigilant attention is defined as ‘‘the capacity to maintain aware responding to routine stimuli and responses while avoiding automaticity and in the absence of external challenge, difficulty, novelty or emotional salience which would otherwise exogenously drive attention to the stimuli in question’’ (Robertson & Garavan, 2004). Vigilant attention is closely linked to one of Posner and Petersen’s (1990) three hypothetical supramodal attentional control systems: the alerting system. According to Posner and Petersen (1990), this is a noradrenergically driven system, which increases the signal-to-noise ratio of target stimuli and thus enhances target detection, albeit at a slightly increased level of false-positives. The locus coeruleus, with its stronger right than left hemisphere innervation (Oke, Keller, Mefford, & Adams, 1978), shows activity which is highly correlated with behavioral performance where monkeys have to detect relatively rare visual targets among foils, but optimal performance is achieved not at maximum levels of locus coeruleus activity, but rather at intermediate levels (Usher, Cohen, Servan-Schreiber, Rajkowski, & Aston-Jones, 1999). The negative effects of noradrengeric depletion on performance in humans can be ameliorated by task difficulty (Arnsten & Contant, 1992), external noise (Smith & Nutt, 1996), and general ‘‘challenge’’ (see Robertson & Garavan, 2004). Vigilant attention therefore represents an attentional capacity that is distinct from the attentional resource conventionally measured in demanding attentional switching or control tasks involving fast responding and working memory load. Furthermore, it is not defined by time on task effects as is often assumed, as the attention to targets in routine situations fluctuates over periods of tens of seconds (Johnson et al., 2007; Whitehead, 1991); the time on task effects originally reported by Mackworth (1968), which occur over periods of tens of minutes, may reflect decreases in the arousal component of the vigilant attention system (Johnson et al., 2007; Paus et al., 1997). Elaborating from Posner and Petersen’s (1990) original concept of the alerting system, the vigilant attention system has two main interacting components: a bottom-up arousal system based in the locus coeruleus, and a top-down attention system based largely in the right dorsolateral prefrontal cortex, with the involvement also of areas of the right parietal cortex. As Paus and his colleagues (1997) have shown, these two systems are involved in vigilant attention, and interact, but are separable (Paus et al., 1997). Declining arousal due to circadian, drug, or brain impairment can be compensated for by the attention system, while bottom-up modulation of the arousal system by drugs, external noise, or challenge can enhance the performance of the right frontoparietal attention system (Robertson & Garavan, 2004).
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Until recently, there was very little evidence from human participants of a linkage between vigilant attention and noradrenergic functioning. Recently our laboratory has shown in healthy people with different dosages of the DBH gene—believed to influence availability of noradrenalin in the cortex—that vigilant attention performance is significantly poorer in people with two copies of the gene (Greene, Bellgrove, Gill, & Robertson, 2009). The right frontoparietal system is a strong candidate for distinguishing aware versus nonaware responses; this has been shown in change blindness studies, where right frontoparietal activation distinguishes stimuli where the change is detected from those where it is not (Beck, Rees, Frith, & Lavie, 2001), and in error processing studies as being a key part of a network that distinguishes errors which are consciously recognized versus those that are not (Hester et al., 2005). The hypothesis advanced in the present chapter—that the vigilant attention system and related error processing have a privileged role in mediating disorders of awareness—is consistent with the many papers that show a prevalence of right frontal pathologies linked to disorders of insight in Alzheimer’s disease (Harwood et al., 2005), post-stroke hemiplegia (Pia, Neppi-Modona, Ricci, & Berti, 2004), and schizophrenia (Shad, Muddasani, & Keshavan, 2006).
‘‘Unskilled and Unaware of It’’: Insight in the Normal Population An intriguingly titled paper ‘‘Unskilled and unaware of it: How difficulties in recognizing one’s own incompetence lead to inflated self-assessments’’ by Kruger and Dunning (1999) is just one of a considerable literature showing that normal, non-brain-impaired populations show consider levels of inaccuracy—usually overestimation—of their levels of attainment and competence across a broad range of domains. Furthermore, those judged objectively to be least competent in a particular domain (for instance, sense of humor) are the least accurate in selfevaluating their level of competence, showing high levels of overestimation. A few other examples of this phenomenon will suffice here: one review (Davis et al., 2006) of self-rated versus objectively assessed competence among physicians throughout the world reported: ‘‘A number of studies found the worst accuracy in self-assessment among physicians who were the least skilled and those who were the most confident.’’ In general there was a very poor relationship between self-rated competence and actual competence. The facts that most drivers consider themselves to be ‘‘above average’’ in driving abilities (McKenna, Stanier, & Lewis, 1991) and that 94% of university/college teachers consider their work to be ‘‘above average’’ (Cross, 1977) drive home a point that is more fully made elsewhere (Dunning, Heath, & Suls, 2004). Kruger and Dunning’s (1999) findings of an inverse relationship between competence and accuracy of self-evaluation is echoed in several other studies and
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the explanation proposed is that incompetence robs people of the metacognitive resources to simultaneously perform the task and monitor their own performance at it. The question for the present chapter is whether we can better define the ‘‘metacognitive resource’’ that may underpin such inaccurate selfassessments. To help address this question, we gave 79 healthy people between the ages of 18 and 53 a battery of neuropsychological tests as well as two self-rating scales: the Frontal Systems Behavior Scale (Grace & Malloy, 2001) and the Cognitive Failures Questionnaire (Broadbent, Cooper, FitzGerald, & Parkes, 1982). Their self-ratings were compared with the ratings of a close relative or friend, and discrepancy scores were calculated. We hypothesized—for the reasons outlined above, namely that online monitoring of performance requires intact vigilant attention to performance—that people who underestimated their level of error and disorganized behavior in everyday life would show impairment on tests of vigilant attention. This is indeed what we found: people who underestimated the level of disorganization in their lives had significantly higher errors on a test of vigilant attention compared to accurate estimators or overestimators (Hoerold et al., 2008). Vigilant attention capacity, as predicted, is correlated with accuracy of selfevaluation. Vigilant attention is also known to be strongly associated with activation of the right dorsolateral prefrontal cortex (Manly et al., 2003; Paus et al., 1997): is this region also associated with accuracy of self-evaluation? In the next section, I will consider evidence from traumatic brain injury (TBI) and localized lesion studies to address this and related questions.
Insight and the Right Dorsolateral Prefrontal Cortex in Neuropsychiatric and Neurological Disorders As Prigatano (see Chapter 12, this volume) has pointed out, TBI can result in a disabling deficit in self-evaluation, which can be a major obstacle to rehabilitation. A proportion of people with TBI underestimate their own deficits in comparison to the ratings of relatives (O’Keeffe, Dockree, & Robertson, 2004), and because of this, TBI self ratings of everyday attentional failures do not correlate with actual attentional performance on assessment; in contrast however, actual performance does correlate with the ratings of attentional failures made by relatives. (Robertson, Manly, Andrade, Baddeley, & Yiend, 1997). As mentioned earlier, adequate vigilant attention—hypothesized in this chapter to be a necessary (but not necessarily sufficient) prerequisite for accurate online self-evaluation—is strongly linked to right dorsolateral prefrontal cortex activation. Is there any evidence that such activation is in turn associated with accurate self-assessment? An fMRI study of TBI individuals showed that indeed there is. Accuracy of self-evaluation was significantly correlated with functional
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activation of the right dorsolateral prefrontal cortex (Schmitz, Rowley, Kawahara, & Johnson, 2006). A recent study from our laboratory comparing people with right versus left prefrontal cortex lesions with posterior lesions found that people with right prefrontal cortex lesions showed significantly lower levels of online awareness of error during a sustained attention task in which they were required to verbally report errors. As a final example, the level of insight in schizophrenia has been shown to be significantly correlated with right dorsolateral prefrontal cortex volume (see Shad et al., 2006, their figure 4). The right dorsolateral prefrontal cortex is strongly linked to impaired self-evaluation across a range of disorders, and this can also be observed in the neurodegenerative conditions the tau-opathies, namely frontotemporal dementia (FTD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP). In a study carried out by my doctoral student Fiadhnait O’Keeffe, it emerged that among these conditions it was in the one most strongly affecting the prefrontal cortex—FTD—that the greatest level of unawareness existed, consistent with the view that unawareness does have a specific relationship to prefrontal cortex functioning. O’Keeffe found that—at around 20%—error awareness among FTD patients was less than half that of CBD and PSP individuals (O’Keeffe, Murray et al., 2007).
Awareness and Arousal The ultimate states of impaired awareness are sleep, intoxication, coma, and death. Sleep, the most benign of these processes, is the end point of a continuum of alertness via various states of drowsiness. Measures of vigilant attention such as the Sustained Attention to Response Task (Robertson et al., 1997) have proved to be the most sensitive measures of degrees of cognitive impairment related to daytime drowsiness (Fronczek, Middelkoop, Dijk, & Lammers, 2006) and, supporting the vigilant attention-arousal-awareness link proposed in this chapter, sleep-related declines in arousal reduce awareness of errors and events (Makeig & Jung, 1996; Tsai, Young, Hsieh, & Lee, 2005). Unilateral spatial neglect can be considered a canonical disorder of awareness. Heilman, Schwartz, and Watson (1978) proposed over 30 years ago that hypoarousal was a key element of neglect—and hence of impaired awareness. A number of studies have shown that arousal is a critical variable associated with level of awareness of the neglected side of space, for instance, showing decreases in awareness with declining levels of arousal (Manly, Dobler, Dodds, & George, 2005). O’Connell et al. (2007) have also shown that electroencephalography arousal measures (theta-beta ratios) correlate 0.48 with error awareness levels across healthy participants. Such correlational studies are supported by research showing a causal link between arousal and awareness. We have shown that unpredictable auditory
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tones without informational value and which transiently increase arousal temporarily reduce—and in some cases abolish—the spatial deficit for about 1 second after their presentation (Robertson, Mattingley, Rorden, & Driver, 1998), this having been replicated in a developmental unilateral spatial neglect (Dobler, Manly, Verity, Woolrych, & Robertson, 2003). Training neglect patients to increase arousal by a self-alerting procedure also improves awareness for the neglected side (Robertson, Tegner, Tham, Lo, & Nimmo-Smith, 1995), and more recently, Manly and his colleagues have shown that the simple expedient of imposing a time limit during a cancellation task greatly improves awareness of the neglected side, likely as a result of the increased arousal induced by the challenge (George, Mercer, Walker, & Manly, 2008). In summary, the arousal component of the vigilant attention system seems to be causally implicated in levels of online awareness.
Role of Error in Mediating Awareness of Deficit How do I know if I am talking too loud, have made a social faux pas, or have behaved absent-mindedly? The most common source of such information is from error: I see the look of discomfort on my interlocutor’s face, or I remember as I close the door that my keys are on the table inside, for example. I may also detect incipient errors before full behavioral execution of them—freezing just as I am about to say something socially insensitive to the person or just catching myself before the door closes. Some states of anosognosia may be exacerbated due to reduced sensory or proprioceptive input, or to disrupted corollary discharge, which shields the person from experiencing the errors that would contribute to their awareness of deficit. But apart from that, people must be sufficiently vigilant as to be able to recognize error as it occurs. Furthermore, the psychophysiological response to error may in turn enhance vigilant attention, possibly via enhanced arousal. Let me consider the evidence for some of these possibilities. If people with impaired prefrontal cortex function arising from FTD or TBI are asked to verbally report when they make an error on simple vigilance tasks, they show a much higher rate of failure to notice errors than do age-matched controls (O’Keeffe, Dockree, Moloney, Carton, & Robertson, 2007; O’Keeffe, Murray et al., 2007) unless the task is unpredictable and challenging, in which case awareness rates in TBI patients is within the normal range (O’Keeffe, Dockree et al., 2007). Furthermore, in the TBI group, there was a significantly reduced electrodermal response to errors, even for errors of which they were fully aware (O’Keeffe et al., 2004). This is also true of another group with impaired prefrontal function—and in particular right prefrontal function (Castellanos et al., 1996)—attention-deficit/hyperactivity disorder (ADHD). O’Connell, Bellgrove, Dockree, and Robertson (2004) have shown that
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ADHD children have reduced electrodermal responses to errors. Among the TBI group, there was also a 0.62 correlation between amplitude of Skin Conductance Response (SCR) to error and the overall level of error awareness.
Conclusions Self-evaluation is the basis for insight, and accurate self-evaluation requires adequate online attention to ongoing performance in the routines of everyday life. The vigilant attention system is the system responsible for this routine monitoring, and it consists of a network that includes two interrelated but independent systems: a locus coeruleus, noradrenalin-based arousal system on the one hand, and a right dorsolateral prefrontal and parietal network on the other. These two subsystems mutually facilitate each other and can compensate for underperformance in the other. Errors are important cues to attention to performance underpinning self-evaluation, and a number of common clinical conditions impairing prefrontal cortex function show impaired error awareness but also impaired arousal response to aware errors. Vigilant attention and awareness share common neuroanatomical underpinnings, and they may be overlapping concepts. Some forms of anosognosia may arise because of reduced error awareness arising from sensory or corollary discharge factors, but impaired vigilant attention, arousal, and associated error responsivity are major factors in poor insight across many different clinical conditions, including TBI, ADHD, schizophrenia, and the tau-opathies, particularly FTD. References Arnsten, A. F. T., & Contant, T. A. (1992). Alpha-2 adrenergic agonists decrease distractibility in aged monkeys performing the delayed response task. Psychopharmacology, 108, 159–169. Barkley, R. A., Murphy, K. R., O’Connell, T., Anderson, D., & Connor, D. F. (2006). Effects of two doses of alcohol on simulator driving performance in adults with attention-deficit/hyperactivity disorder. Neuropsychology, 20(1), 77–87. Beck, D. M., Rees, G., Frith, C. D., & Lavie, N., (2001). Neural correlates of change detection and change blindness. Nature Neuroscience, 4, 645–650. Broadbent, D. B., Cooper, P. F., FitzGerald, P., & Parkes, K. R. (1982). The Cognitive Failures Questionnaire (CFQ) and its correlates. British Journal of Clinical Psychology, 21, 1–16. Castellanos, F. X., Giedd, J. N., Marsh, W. L., Hamburger, S. D., Vaituzis, A. C., Dickstein, D. P., et al. (1996). Quantitative brain magnetic-resonance-imaging in attention-deficit hyperactivity disorder. Archives of General Psychiatry, 53(7), 607–616. Cross, P. (1977). Not can but will college teaching be improved. New Directions for Higher Education, 17, 1–15.
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Davis, D. A., Mazmanian, P. E., Fordis, M., Van Harrison, R., Thorpe, K. E., & Perrier, L. (2006). Accuracy of physician self-assessment compared with observed measures of competence: A systematic review. Journal of the American Medical Association, 296(9), 1094–1102. Dobler, V., Manly, T., Verity, C., Woolrych, J., & Robertson, I. H. (2003). Modulation of spatial attention in a child with developmental unilateral neglect. Developmental Medicine & Child Neurology, 45(4), 282–288. Dunning, D., Heath, C., & Suls, J. M. (2004). Flawed self-assessment: Implications for health, education, and the workplace. Psychological Science in the Public Interest, 5(3), 69–106. Fischer, H., Wik, G., & Fredrikson, M. (1997). Extraversion, neuroticism and brain function: A PET study of personality. Personality and Individual Differences, 23(2), 345–352. Fronczek, R., Middelkoop, H., Dijk, J. V., & Lammers, G. (2006). Focusing on vigilance instead of sleepiness in the assessment of narcolepsy: High sensitivity of the Sustained Attention to Response Task (SART). Sleep, 29, 187–191. George, M. S., Mercer, J. S., Walker, R., & Manly, T. (2008). A demonstration of endogenous modulation of unilateral spatial neglect: The impact of apparent timepressure on spatial bias. Journal of the International Neuropsychological Society, 14, 33–41. Grace, J., & Malloy, P. (2001). Frontal Systems Behavior Scale professional manual. Lutz: Florida: Psychological Assessment Resources. Greene, C., Bellgrove, M. A., Gill, M., & Robertson, I. H. (2009). Noradrenergic genotype predicts lapses in sustained attention. Neuropsychologia, 47, 591–594. Gusnard, D. A., Akbudak, E., Shulman, G. L., & Raichle, M. E. (2001). Medial prefrontal cortex and self-referential mental activity: Relation to a default mode of brain function. Proceedings of the National Academy of Sciences, USA, 98, 4259–4264. Haas, B. W., Constable, R. T., & Canli, T. (2008). Stop the sadness: Neuroticism is associated with sustained medial prefrontal cortex response to emotional facial expressions. NeuroImage, 42(1), 385–392. Harwood, D. G., Sultzer, D. L., Feil, D., Monserratt, L., Freedman, E., & Mandelkern, M. A. (2005). Frontal lobe hypometabolism and impaired insight in Alzheimer disease. American Journal of Geriatric Psychiatry, 13(11), 934–941. Heilman, K. M., Schwartz, H. D., & Watson, R. T. (1978). Hypoarousal in patients with the neglect syndrome and emotional indifference. Neurology, 28(3), 229–232. Hester, R., Foxe, J. J., Molholm, S., Shpaner, M., & Garavan, H. (2005). Neural mechanisms involved in error processing: A comparison of errors made with and without awareness. NeuroImage, 27(3), 602–608. Hoerold, D., Dockree, P., O’Keeffe, F., Bates, H., Pertl, M., & Robertson, I. (2008). Neuropsychology of self-awareness in young adults. Experimental Brain Research, 186(3), 509–515. Johnson, K. A., Kelly, S. P., Bellgrove, M. A., Barry, E., Cox, M., Gill, M., et al. (2007). Response variability in attention deficit hyperactivity disorder: Evidence for neuropsychological heterogeneity. Neuropsychologia, 45, 630–638. Johnson, S. C., Baxter, L. C., Wilder, L. S., Pipe, J. G., Heiserman, J. E., & Prigatano, G. P. (2002). Neural correlates of self-reflection. Brain, 125, 1808–1814.
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Kruger, J., & Dunning, D. (1999). Unskilled and unaware of it: How difficulties in recognizing one’s own incompetence lead to inflated self-assessments. Journal of Personality and Social Psychology, 77, 1121–1134. Leahy, R. L. (2005). Clinical implications in the treatment of mania: Reducing risk behavior in manic patients. Cognitive and Behavioral Practice, 12(1), 89–98. Mackworth, J. F. (1968). Vigilance, arousal and habituation. Psychological Review, 75, 308–322. Makeig, S., & Jung, T.-P. (1996). Tonic, phasic, and transient EEG correlates of auditory awareness in drowsiness. Cognitive Brain Research, 4(1), 15–25. Manly, T., Dobler, V. B., Dodds, C. M., & George, M. A. (2005). Rightward shift in spatial awareness with declining alertness. Neuropsychologia, 43(12), 1721–1728. Manly, T., Owen, A. M., Datta, A., Lewis, G., Scott, S., Rorden, C., et al. (2003). Enhancing the sensitivity of a sustained attention task to frontal damage. Convergent clinical and functional imaging evidence. Neurocase, 9, 340–349. Manly, T., Robertson, I. H., Galloway, M., & Hawkins, K. (1999). The absent mind: Further investigations of sustained attention to response. Neuropsychologia, 37(6), 661–670. McKenna, F. P., Stanier, R. A., & Lewis, C. (1991). Factors underlying illusory selfassessment of driving skill in males and females. Accident Analysis and Prevention, 23, 45–52. O’Connell, R. G., Bellgrove, M. A., Dockree, P. M., & Robertson, I. H. (2004). Reduced electrodermal response to errors predicts poor sustained attention performance in attention deficit hyperactivity disorder. Neuroreport, 15, 2535–2538. O’Connell, R. G., Dockree, P. M., Bellgrove, M. A., Kelly, P. S., Hester, R., Garavan, H., et al. (2007). The role of cingulate cortex in the detection of errors with and without awareness: A high-density electrical mapping study. European Journal of Neuroscience, 25(8), 2571–2579. O’Keeffe, F. M., Dockree, P. M., Moloney, P., Carton, S., & Robertson, I. H. (2007). Characterising error-awareness of attentional lapses and inhibitory control failures in patients with traumatic brain injury. Experimental Brain Research, 180, 59–67. O’Keeffe, F. M., Dockree, P. M., & Robertson, I. H. (2004). Poor insight in traumatic brain injury mediated by impaired error processing? Evidence from electrodermal activity. Cognitive Brain Research, 22, 101–112. O’Keeffe, F. M., Murray, B., Coen, R. F., Dockree, P. M., Bellgrove, M. A., Garavan, H., et al. (2007). Loss of insight in frontotemporal dementia, corticobasal degeneration and progressive supranuclear palsy. Brain, 130(3), 753–764. Oke, A., Keller, R., Mefford, I., & Adams, R. (1978). Lateralization of norepinephrine in human thalamus. Science, 200, 1411–1413. Paus, T., Zatorre, R. J., Hofle, N., Caramanos, Z., Gotman, J., Petrides, M., et al. (1997). Time-related changes in neural systems underlying attention and arousal during the performance of an auditory vigilance task. Journal of Cognitive Neuroscience, 9, 392–408. Pia, L., Neppi-Modona, M., Ricci, R., & Berti, A. (2004). The anatomy of anosognosia for hemiplegia: A meta-analysis. Cortex, 40, 367–377. Posner, M. I., & Petersen, S. E. (1990). The attention system of the human brain. Annual Review of Neuroscience, 13, 25–42.
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Robertson, I. H., & Garavan, H. (2004). Vigilant attention. In M. S. Gazzaniga (Ed.), The Cognitive neurosciences (3rd edition, pp. 563–578). Cambridge, MA: MIT Press. Robertson, I. H., Manly, T., Andrade, J., Baddeley, B. T., & Yiend, J. (1997). Oops! Performance correlates of everyday attentional failures in traumatic brain injured and normal subjects: The Sustained Attention to Response Task (SART). Neuropsychologia, 35, 747–758. Robertson, I. H., Mattingley, J. B., Rorden, C., & Driver, J. (1998). Phasic alerting of neglect patients overcomes their spatial deficit in visual awareness. Nature, 395(10), 169–172. Robertson, I. H., Tegner, R., Tham, K., Lo, A., & Nimmo-Smith, I. (1995). Sustained attention training for unilateral neglect: Theoretical and rehabilitation implications. Journal of Clinical and Experimental Neuropsychology, 17, 416–430. Sachdev, P., Mondraty, N., Wen, W., & Gulliford, K. (2008). Brains of anorexia nervosa patients process self-images differently from non-self-images: An fMRI study. Neuropsychologia, 46(8), 2161–2168. Schmitz, T. W., Rowley, H. A., Kawahara, T. N., & Johnson, S. C. (2006). Neural correlates of self-evaluative accuracy after traumatic brain injury. Neuropsychologia, 44(5), 762–773. Shad, M. U., Muddasani, S., & Keshavan, M. S. (2006). Prefrontal subregions and dimensions of insight in first-episode schizophrenia—A pilot study. Psychiatry Research: Neuroimaging, 146(1), 35–42. Smith, A., & Nutt, D. (1996). Noradrenaline and attention lapses. Nature, 380, 291. Tsai, L.-L., Young, H.-Y., Hsieh, S., & Lee, C.-S. (2005). Error monitoring after sleep deprivation. Sleep, 28, 707–713. Usher, M., Cohen, J. D., Servan-Schreiber, D., Rajkowski, J., & Aston-Jones, G. (1999). The role of locus coeruleus in the regulation of cognitive performance. Science, 283, 549–553. Voelz, Z. R., Walker, R. L., Pettit, J. W., Joiner Jr., T. E., & Wagner, K. D. (2003). Depressogenic attributional style: Evidence of trait-like nature in youth psychiatric inpatients. Personality and Individual Differences, 34(7), 1129–1140. Whitehead, R. (1991). Right hemisphere processing superiority during sustained visual attention. Journal of Cognitive Neuroscience, 3, 329–335.
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16
Emotional Awareness among Brain-Damaged Patients Ricardo E. Jorge
More than a century ago, Babinski coined the term anosognosia to describe the puzzling presentation of patients who were unaware of their motor deficits associated with stroke. A similar phenomenon was also described among patients suffering from cortical blindness and other sensory deficits (Bisiach, Vallar, Perani, Papagno, & Berti, 1986). From its inception, it was clear that anosognosia could not be adequately explained purely on the basis of psychological terms and was related to the disruption of specific neural circuits in the brain (Heilman, Barrett, & Adair, 1998; Orfei et al., 2007; Ramachandran, 1996). More recently, this eminently neurological approach was applied to describe unawareness of deficits in other domains, such as memory and executive functions, as well as in complex processes regulating decision making and social interaction (Bechara, Damasio, Tranel, & Damasio, 1997, 2005; Boake, Freeland, Ringholz, Nance, & Edwards, 1995; Damasio, 1996; Levine, Calvanio, & Rinn, 1991; McGlynn & Schacter, 1989; Schacter, 1990). In addition, the spectrum of structural alterations of the brain was expanded to include traumatic injuries (Giacino & Cicerone, 1998; Hoofien, Gilboa, Vakil, & Barak, 2004; Prigatano & Schacter, 1991) and neurodegenerative disorders such as Alzheimer’s disease (Souchay, 2007; Starkstein et al., 1996), Huntington’s disease (Hoth et al., 2007), and frontotemporal dementia (Eslinger et al., 2005; Ruby et al., 2007; Salmon et al., 2008). In the realm of psychiatry, loss of insight was a decisive criterion in the early conceptualization of mental illness, particularly with regard to major psychosis. During the last half of the nineteenth century, however, psychiatric investigators became aware that patients with psychiatric disorders varied with regard to the degree of awareness of their cognitive, volitional, and emotional deficits (Berrios, 1996). Later, at the time when the psychiatric field was revolutionized by the formulation of the psychoanalytic theory (Freud & Brill, 1938), awareness 333
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and insight were interpreted on the basis of psychodynamic concepts and defense mechanisms. However, both the neurological and psychiatric disciplines converge in the assumption that the clinical phenomena subsumed under the notions of unawareness, insight, and denial have significant prognostic and therapeutic implications and that their presence has a detrimental effect on patients’ recovery. Defining multidimensional concepts such as anosognosia, awareness of emotions, and insight is certainly a challenging task. For instance, although there is agreement with regard to the fact that these phenomena occur along a continuum and are better described within a dimensional perspective, it is unclear whether a categorical diagnosis would provide a more meaningful understanding of their functional repercussion, clinical course, and long-term prognosis (Markova & Berrios, 1995; Markova, Clare, Wang, Romero, & Kenny, 2005). In addition, investigators in this field have enriched the conceptual discussion of these phenomena by the identification of important differences between awareness and attribution processes (Russell, 2003), explicit versus implicit features (Lane, Ahern, Schwartz, & Kaszniak, 1997), as well as the opposition of intellectual and emotional awareness developed in the psychoanalytic tradition (Alford & Beck, 1994). Markova and Berrios (1995) remind us that insight is an intentional concept and thus implies a specific object. In turn, the nature of this object will determine the clinical phenomenon and the method employed to assess it. This is particularly relevant in the case of emotions and affective symptoms, which are more difficult to be identified, described, and eventually measured. Consequently, operational definitions and quantitative assessments of unawareness are much more developed in the neurological and neuropsychological terrains than in the psychiatric arena. For instance, there are very few instruments assessing insight of affective illness, none of them with a clear-cut demonstration of their validity (Sturman & Sproule, 2003). Studying mood disorders that occur in the aftermath of brain damage adds further complexity to this problem. Although multiple etiological factors contribute to the emergence of these types of mood disorders, it is accepted that the disruption of specific distributed neural networks encompassing the prefrontal cortex and the medial temporal lobe plays an important causal role and modifies their clinical presentation. For instance, mood disorders associated with cerebrovascular disease are characterized by the frequent occurrence of executive impairment and apathetic features. Insight and awareness of affective deficits are clinical phenomena that have been rarely studied among brain-injured patients and their neurobiological mechanism is largely unknown. However, we can hypothesize that abnormality in emotional regulation and metacognitive functions would have distinct clinical presentation among depressed patients with coexistent brain damage. An extensive analysis of the psychological concepts related to emotional processing as well as a portrayal of the unrelenting progress of affective
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neuroscience research are clearly out of the scope of this chapter. However, I will briefly describe the constructs of emotional awareness and alexithymia, as well as the instruments that have been commonly used to assess them. Finally, I review recent studies on alexithymia associated with stroke and traumatic brain injury and report preliminary results of our work on this topic.
Emotional Awareness and Alexithymia To some extent, the current conceptualization of emotional processing was foreshadowed by the work of two major figures of psychological thought: William James and Ludwig Wittgenstein. James was among the first to emphasize the importance of somatic and autonomic sensory feedback, and of the resulting cortical representation of body states in the physiology of feelings and emotions. He also suggested that emotional experiences play a decisive role in modeling behavior (James, 1890). Although Wittgenstein was critical of many aspects of James’ work (e.g., the method of introspection and the notion of an ostensive definition of psychological concepts), he acknowledged the importance of what became known as the James-Lange theory. However, Wittgenstein and Anscombe (1953) emphasized the importance of linguistic processing and of what he called language games in the delimitation of psychological concepts. Furthermore, according to his view, language is ultimately the expression of a particular form of life; it depends and develops on the basis of the interaction with the material and cultural aspects of our world (Wittgenstein & Anscombe, 1953). Language and other forms of symbolic representation become inextricably associated with the representation and expression of emotions, dissecting them as an anatomist and modeling them as a sculptor. In addition, Wittgenstein’s emphasis on the interactive (social) experiential aspects of language acquisition connotes the developmental nature of emotional awareness. Functional neuroimaging studies on linguistic processing of emotional information have demonstrated that affect labeling modifies the limbic response to negative emotional images. In contrast to gender labeling of pictures, affect labeling increases activity in areas of the right prefrontal cortex, specifically the right ventrolateral prefrontal cortex and the medial prefrontal cortex. Furthermore, the fact that activity in these regions is inversely correlated with amygdala activity suggests that linguistic processing of emotions modulates more basic affective responses (Creswell, Way, Eisenberger, & Lieberman, 2007; Lieberman et al., 2007). More recent studies from the same investigators showed that repeated exposure to labeled aversive images produces greater autonomic reactivity attenuation than repeated exposure to nonlabeled aversive images. In addition, this greater attenuation is also observed 8 days after the initial exposure, even when the aversive stimuli were presented without their labels (Tabibnia, Lieberman, & Craske, 2008).
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Interestingly, more than three decades ago, Sifneos et al. (1973) introduced the concept of alexithymia (literally without words for mood) to define an alteration in emotional processing characterized by the difficulty in identifying emotions and differentiating them from other physical states, difficulty in describing emotions, limited ability to represent or fantasize scenarios with significant emotional content, and a concrete cognitive style that disregards the complex emotional, motivational, and symbolic aspects of human behavior (Apfel & Sifneos, 1979; Sifneos, 1973, 1996; Taylor, Bagby, & Parker, 1993; Weinryb, Gustavsson, Asberg, & Rossel, 1992). Alexithymic patients show altered processing of emotional information (e.g., the ability to identify facial expressions) (Parker, Taylor, & Bagby, 1993; Roedema & Simons, 1999) and deficient modulation of emotional responses that may result in impulsive behavior (Taylor & Bagby, 2004). In addition, alexithymia has been associated with changes in major personality dimensions, such as increased neuroticism and decreased openness to new experiences (Bagby, Taylor, & Parker, 1994). It has also been suggested that patients with alexithymia have a limited capacity to enjoy pleasurable and gratifying experiences (i.e., they tend to be anhedonic), as well as severe impairment in coping with stress (Bagby, Taylor, & Parker, 1994; Loas et al., 1998; Luminet, Bagby, Wagner, Taylor, & Parker, 1999). Furthermore, alexithymic patients are prone to express psychological distress in the form of somatic symptoms and, thus, are more vulnerable to develop psychosomatic disorders (Taylor, Bagby, & Parker, 1991). Finally, regarding the relationship of alexithymia with mental illness, previous studies have reported the presence of alexithymic features among patients with diverse psychopathological conditions such as depressive disorders (Marchesi, Bertoni, Cantoni, & Maggini, 2008; Saarijarvi, Salminen, & Toikka, 2006), post-traumatic stress disorder (Frewen, Pain, Dozois, & Lanius, 2006; Kupchik et al., 2007; Yehuda et al., 1997), eating disorders (Taylor, Parker, Bagby, & Bourke, 1996), and Cluster B personality disorders (Guttman & Laporte, 2002; Sayar, Ebrinc, & Ak, 2001). There are several instruments designed to give a quantitative estimation of alexithymia. At the present time, the Toronto Alexithymia Scale (TAS) is the most widely used assessment device, with the most rigorous psychometric validation. A revised version consisting of 20 items (TAS-20) that cluster in three main factors has been consistently replicated in independent samples of healthy controls and various clinical populations (Bagby, Taylor, & Parker, 1994; Parker, Taylor, Bagby, & Thomas, 1991; Taylor, Bagby, & Parker, 2003). The first factor corresponds to the ability to identify emotions, the second factor is related to the ability to describe emotions, and the third factor assesses the concrete cognitive style observed among alexithymic patients. There is some controversy regarding the stability of the alexithymia construct and whether TAS-20 scores have significant correlations with conventional measures of the severity of depressive and anxious symptoms (de Timary, Luts, Hers, &
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Luminet, 2008; Honkalampi, Hintikka, Saarinen, Lehtonen, & Viinamaki, 2000; Marchesi, Bertoni, Cantoni, & Maggini, 2008; Marchesi, Brusamonti, & Maggini, 2000; Subic-Wrana, Bruder, Thomas, Lane, & Kohle, 2005). Overall, the available evidence on this issue suggests that alexithymia, depression and anxiety are related but ultimately independent constructs with a different longitudinal course (Marchesi, Brusamonti, & Maggini, 2000). Finally, we must keep in mind that we can use a cut-off score on the TAS-20 scale in order to make a categorical diagnosis of alexithymia. Lane, Quinlan, Schwartz, Walker, and Zeitlin (1990) have taken a different approach to assess awareness of emotions that resulted in the development of the Level of Emotional Awareness Scale (LEAS) (Lane et al., 1990). Rather than relying on self-reported information, as in the case of TAS-20, the LEAS attempts to objectively probe the extent and quality of emotional awareness. Basically, when completing this instrument, subjects are required to describe their feelings, as well as those of another person in response to different scenarios depicted in 20 vignettes of two to four sentences. The scoring system evaluates the structure of the experience focusing on the specificity, variety, and range of the emotional words used, as well as the degree of understanding of the different perspectives of the subjects involved in a particular situation. Of note, LEAS scores do not correlate with self-reported negative affect in the absence of anxiety or depressive disorders (Subic-Wrana et al., 2005). Greater emotional awareness is associated with greater impulse control consistent with a top-down regulation of more basic and implicit emotional responses. Consistent with this notion, patients with borderline personality disorder present lower LEAS scores (Levine, Marziali, & Hood, 1997). In addition, patients with PTSD (Frewen et al., 2008) and patients with psychosomatic disorders (Subic-Wrana et al., 2005) present lower LEAS scores than healthy controls. Lane et al. (1990) used positron emission tomography (PET)—based emotional activation paradigms to identify brain regions that correlated with emotional awareness as measured by LEAS scores (Lane et al., 1998). They concluded that, in the case of visually induced emotion, LEAS scores showed a positive correlation with an activation cluster located in right midcingulate cortex, while for recall-induced emotion the region that showed the highest correlation with LEAS scores was the right anterior cingulate cortex (ACC). More important, both clusters overlapped in a discrete region of the dorsal ACC in the right hemisphere (Lane et al., 1998). A second study by the same group reported that these significant correlations were mainly observed in high arousal conditions and were greater for women (McRae, Reiman, Fort, Chen, & Lane, 2008). As a result of research conducted with the help of the LEAS, and inspired by the work of Paul MacLean (1977, 1985), Lane (2008) proposed a hierarchical model of emotional awareness that was meant to provide a general framework for the study of psychosomatic illness (Lane, 2008). He emphasizes the
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developmental nature of this process and the progressive integration of specific schemata that configure emotional experience. According to Lane’s (2008) model, emotional awareness develops through five levels of increasing complexity: awareness of physical sensations, action tendencies, single emotions, blend of emotions, and, finally, blends of blends of emotional experience. The first two levels rely on implicit (unconscious) processing of emotionally laden stimuli, while the remaining three levels correspond to a progressively complex explicit (conscious) elaboration of emotional experiences. This model distinguishes between the neural components of implicit processing (e.g., the thalamus and the amygdala) (Doron & Ledoux, 1999; Doyere, Debiec, Monfils, Schafe, & LeDoux, 2007; Phelps, Delgado, Nearing, & LeDoux, 2004; Phelps & LeDoux, 2005; Rogan, Staubli, & LeDoux, 1997) and three components of the conscious experience of emotion: background feelings, focal attention to feelings, and reflective awareness. Background feelings give the basic emotional color to our experience, but they are not the focus of our attention (Damasio, 2003; Kawasaki et al., 2005). They are probably integrated in circuits that include, among other regions, structures that process interoceptive information such as the subgenual and pregenual ACC, the anterior insula, and the somatosensory associative areas in the parietal cortex of the right hemisphere (Adolphs, Damasio, Tranel, Cooper, & Damasio, 2000; Anderson & Phelps, 2002; Bechara, Damasio, Tranel, & Damasio, 2005; Damasio, 1996; Mesulam & Mufson, 1982). Attention to feelings and the activation of linguistic processing have been associated with the function of the dorsal ACC, a region known to mediate controlled rather than automatic behavioral responses, as well as error monitoring (Botvinick, Nystrom, Fissell, Carter, & Cohen, 1999; Brown & Braver, 2005; Bush et al., 2002; Carter et al., 1998; Critchley, 2005; Critchley, Wiens, Rotshtein, Ohman, & Dolan, 2004; Frankland, Bontempi, Talton, Kaczmarek, & Silva, 2004; Kalisch, Wiech, Critchley, & Dolan, 2006; Kerns et al., 2004; Sharot, Riccardi, Raio, & Phelps, 2007; Wang et al., 2005; Yamasaki, LaBar, & McCarthy, 2002). Finally, reflective awareness of emotions implies further cognitive operations on the emotional information that is proposed to be conducted in those prefrontal circuits that have evolved and specialized to represent mental states of the self and of others (i.e., theory of mind processes), particularly those involving the dorsomedial prefrontal cortex. The complex representation of these states corresponds to higher levels of emotional awareness and will modify the processing of ulterior emotional stimuli (D’Argembeau et al., 2007; Moran, Macrae, Heatherton, Wyland, & Kelley, 2006; Ochsner et al., 2004; Spreng, Mar, & Kim, 2008).
Alexithymia in Stroke Disturbances of emotional perception and emotional expression associated with neurological illness have been studied for several decades. For instance, Tucker
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et al. (1977) reported that patients with right hemisphere damage (RHD) demonstrated defective emotional prosody (Tucker, Watson, & Heilman, 1977). This finding was replicated in a large number of empirical studies and aprosodia has been accepted as a relatively frequent neuropsychiatric complication of stroke (Borod et al., 2000; Heilman, Leon, & Rosenbek, 2004; Leon et al., 2005; Ross, Harney, deLacoste-Utamsing, & Purdy, 1981; Ross, Thompson, & Yenkosky, 1997). More recently, Bloom, Borod, Obler, and Gerstman (1992) observed that, when asked to describe emotional laden slides, patients with RHD elicited words of significantly less emotional content than patients with left hemisphere damage (LHD) or healthy controls (Bloom et al., 1992). Similarly, Borod et al. (1996) compared the discourse of patients with RHD, LHD, and normal volunteers and concluded that the emotional content of the discourse of subjects with RHD was significantly less than that observed among patients with LHD or controls (Borod et al., 1996). Other investigators, however, were not able to replicate these findings. For example, Blonder et al. (2005) reported opposite results when comparing the percentage of emotional words in the discourse of 14 aphasic patients (LHD) and 9 patients with aprosodia (RHD). These authors suggest that the deficits in emotional expression observed in patients with RHD are related to abnormalities in the encoding of nonverbal emotional expression rather than the inability to experience or conceptualize emotions (Blonder et al., 2005). The latter is consistent with previous clinical studies reporting that the frequency of major depression is not significantly different in stroke patients with anosognosia compared with stroke patients without anosognosia (Starkstein, Berthier, Fedoroff, Price, & Robinson, 1990). An empirical evaluation of the alexithymia construct has rarely been done in the context of structural brain damage. However, early studies in cerebral commissurotomy patients proposed that alexithymia resulted from deficits in interhemispheric transfer of information by which emotional experiences integrated in the right hemisphere cannot access linguistic processing circuits located in the left (TenHouten, Hoppe, Bogen, & Walter, 1986). Recently, Spaletta et al. (2001) used the TAS-20 to assess alexithymic features in a group of 48 stroke patients, 21 with RHD and 27 with LHD (Spalletta et al., 2001). After controlling for the level of cognitive impairment and the severity of depression and anxiety symptoms, TAS-20 scores were significantly higher among patients with RHD, an effect driven by significantly higher scores in Factor 1 (identify emotions) and Factor 2 (describe emotions) of the TAS-20 scale. There was also a gender by side interaction by which men with RHD had significantly higher TAS-20 scores than men with LHD. Significant lateralized differences were not observed among women. Overall, these findings suggest that alexithymia may be a good indicator of unawareness of emotions among patients with stroke (Spalletta et al., 2001). The same group of investigators examined whether alexithymia overlapped with unawareness of motor deficits (anosognosia) in an independent sample of 50 firstever stroke patients with RHD (Spalletta et al., 2007). Alexithymia was diagnosed
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using a cut-off score in the TAS-20 (scores equal or greater than 61 determined a positive diagnosis) while anosognosia was assessed using the Bisiach Anosognosia Scale and neglect was evaluated through the neurological examination and appropriate neuropsychological tests such as the Line Bisection Test (Friedman, 1990). Of the 50 patients included in the study, 26% patients had anosognosia, 52% presented with neglect, and 52% were diagnosed as alexithymic. More important, there were cases where alexithymia occurred independently from anosognosia, suggesting that these conditions are mediated by different, although probably overlapping neural circuits. Consistent with this notion, patients with coexistent alexithymia and anosognosia had more extensive lesions and greater frontal dysfunction than patients with alexithymia without anosognosia (Spalletta et al., 2007). Finally, these investigators have examined the clinical course of 50 patients with poststroke depression to determine whether TAS-20 scores that correspond to the three alexithymia factors change with antidepressant treatment (Spalletta, Ripa, Bria, Caltagirone, & Robinson, 2006). Out of these 50 patients, 18 had coexistent alexithymia while the remaining 32 patients were not alexithymic. As expected, a diagnosis of alexithymia was significantly associated with RHD. Patients with an alexithymia diagnosis showed a significant decline of Factor 1 and Factor 2 scores associated with antidepressant treatment. Such a decline was not observed in the group of patients without alexithymia. Interestingly, the change in the TAS-20 scores did not correlate with the change in Hamilton Depression Rating Scale (HDRS) scores and, thus, was not related to the magnitude of the antidepressant response (Spalletta et al., 2006). It is unclear whether changes in the activation of mood regulation areas associated with the effect of antidepressants (e.g., different areas of the cingulate cortex) contribute to the change in TAS-20 scores. Although alexithymia has been consistently associated with RHD among patients with stroke, little has been done to further identify the lateralized circuits mediating emotional awareness. A recent report, however, described the case of a 61-year-old woman with an ischemic stroke in the territory of the right pericallosal artery who presented with reduced emotional responsiveness, impaired affect recognition, and prominent alexithymic features (TAS-20 score was 62) (Schafer et al., 2007). Magnetic resonance imaging (MRI) showed a lesion of the right ACC and the anterior corpus callosum that involved the dorsal ACC and extended into the ventral aspect of the medial superior frontal gyrus (Schafer et al., 2007). This is consistent with the model of emotional awareness previously described.
Alexithymia in Traumatic Brain Injury Background There are several reports on the association of traumatic brain injury (TBI) and alexithymia. Williams et al., evaluated 135 outpatients in a family practice
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setting for the presence of both TBI and alexithymia. They observed that those patients who had a positive history of TBI had significantly higher TAS-20 scores than patients without a history of TBI (Williams et al., 2001). Koponen et al. (2005) compared the frequency of alexithymia between 54 chronic TBI patients and a control group of similar demographic characteristics and comparable severity of depressive symptoms. Alexithymia was significantly more frequent among the TBI group (Odds Ratio ¼ 2.64, Confidence Interval ¼ 1.03—6.80) and was associated with greater psychopathology (Koponen et al., 2005). Another recent study by Henry, Phillips, Crawford, Theodorou, and Summers (2006) compared a group of 28 subjects with severe TBI with 31 healthy control subjects on the different factors of the TAS-20, self-reported measures of depression, anxiety, and quality of life, as well as fluency tasks of different complexity (Henry et al., 2006). As expected, TBI patients showed greater levels of alexithymia than controls. There was a strong association between the TAS-20 Factor 1 (identify emotions) and Factor 2 (describe emotions) and self-report measures of anxiety, depression, and quality of life. After controlling for the substantial effect of depression and anxiety symptoms, difficulty to identify emotions (Factor 1) was associated with reduced quality of life. This factor was the only variable related to deficit in executive functioning (Henry et al., 2006). Finally, Wood and Williams (2007) examined the prevalence and correlates of alexithymia in a larger group of TBI patients (n ¼ 121) compared with 52 patients with orthopedic injuries. These investigators confirmed the higher frequency of alexithymia in the TBI group compared with the control group, as well as the presence of moderate correlations between TAS-20 scores and selfreport measures of anxiety and depression. However, regression analysis revealed that depression and anxiety scores explained a small percentage of the variance in TAS-20 scores, suggesting that these constructs are overlapping, albeit distinct, constructs in the TBI population. There was not a significant association between alexithymia and severity of brain injury or executive dysfunction (Wood & Williams, 2007). For the past few years we have studied the prevalence, duration, and clinical correlates of mood and anxiety disorders following TBI. Further details of this work can be found elsewhere (Jorge, 2005; Jorge et al., 2004; Jorge et al., 2005). In this chapter we will report our preliminary findings on alexithymia following TBI, as assessed with the use of the TAS-20.
Methods Participants consisted of 91 consecutive patients with closed head injury admitted to the University of Iowa Hospitals and Clinics, Iowa City (n ¼ 60) or the Iowa Methodist Medical Center, Des Moines (n ¼ 31). Patients with penetrating head injuries or those with clinical or radiological findings suggesting spinal cord injury were excluded from the study. Sixty-eight (74.7%)
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of the 91 patients with TBI were injured in a motor vehicle collision, 16 patients (17.6%) by a fall, 3 patients (3.3%) by assault, and 4 patients (4.4%) by other mechanisms (e.g., sport-related injuries). Severity of TBI was assessed using the 24-hour Glasgow Coma Scale (GCS) score (Teasdale & Jennett, 1976). The overall severity of the traumatic injury was assessed using the Abbreviated Injury Scale (MacKenzie, Shapiro, & Eastham, 1985). Using initial GCS scores and computed tomographic data, 40 patients (44.3%) were classified as mild TBI, 30 patients (32.5%) with moderate TBI, and 21 patients (23.2%) with severe TBI. The TAS-20 was included as part of the assessment battery several months after the study was initiated. Of the 91 TBI patients who were initially enrolled in this study, 74 (81.3%) completed the TAS-20 and constitute our study group. Psychiatric assessment was conducted using the Structured Clinical Interview for DSM-IV diagnoses (Williams et al., 1992). Severity of depressive and anxiety symptoms were assessed using the Hamilton Depression Rating Scale (HDRS) (Hamilton, 1960) and the Hamilton Anxiety Scale (HARS) (Hamilton, 1959), respectively. Aggressive behavior was assessed using a modified version of the Overt Aggression Scale (OAS) (Silver & Yudofsky, 1991). To be categorized as aggressive, a patient had to have at least four episodes of significant aggressive behavior during the previous month and have an aggression score of 3 or more on the OAS. As aforementioned, the TAS-20 was used to evaluate alexithymic features. Scores equal or greater than 61 on this scale were considered indicative of alexithymia diagnosis. The Mini-Mental State Examination (MMSE) (Folstein, Folstein, & McHugh, 1975) was used as a global measure of cognitive functioning. Impairment in activities of daily living was assessed using the Functional Independence Measure (Forer & Granger, 1987). Psychosocial adjustment was quantitatively assessed using the Social Functioning Examination and Social Ties Checklist (Starr, Robinson, & Price, 1983). Neuropsychological assessment focused on memory and frontal-executive functioning, as assessed by the following six tests: Rey Auditory Verbal Learning Test (delayed recall trial) (Rey, 1964); Rey Complex Figure Test (delayed recall trial) (Rey, 1964); Trail Making Test (Time B) (Reitan, 1971); Multilingual Aphasia Examination (Controlled Oral Word Association Test total score) (Benton, Hamsher, & Sivan, 1994); Stroop Color-Word Interference Test (Golden, 1978); and Wisconsin Card-Sorting Test (the number of perseverative errors) (Heaton, Chelune, & Tailey, 1993). In addition, a research MRI was obtained in a subgroup of these patients (n ¼ 31) using a 1.5-Tesla scanner at the radiology department of the University of Iowa. The tools of a locally developed software package, BRAINS-2 (Department of Psychiatry, University of Iowa) were used to generate volumetric data (Andreasen et al., 1996). The validity and reproducibility of morphometric analysis using the aforementioned software has been reported
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in previous studies (Magnotta et al., 1999; Magnotta et al., 2002). In addition, the ACC was traced on segmented coronal images simultaneously inspecting the other image planes and surface reconstruction (McCormick et al., 2006). The ACC was further subdivided into four architectonically and functionally distinct sectors: dorsal, rostral, subcallosal, and subgenual (McCormick et al., 2006).
Results Of the 74 patients included in this study, 17 (23%) met diagnostic criteria for alexithymia and were included in the alexithymia group (Alex), while the remaining 57 TBI patients were included in the nonalexithymia group (No-Alex). The background characteristics of both groups are summarized in Table 16.1. There were no differences between the Alex and the No-Alex groups in age, gender, socioeconomic status, and educational level or unemployment rates. In addition, there were not significant differences in the severity of brain injury, activities of daily living impairment, or social functioning. Psychiatric findings are summarized in Table 16.2. When compared with the No-Alex group, ALEX patients had significantly higher frequency of alcohol misuse (Fisher Exact Test, p ¼ 0.0225), drug misuse (Fisher Exact Test, p ¼ 0.027), and aggressive behavior (Fisher Exact Test, p ¼ 0.0117). We did not observe significant differences between the Alex and the No-Alex groups in the frequency of major depression or anxiety disorder with generalized features. In addition, we did not find significant differences between the groups in the severity of anxiety or depressive symptoms. We examined the correlation between TAS-20 total and factor scores with both HDRS and HARS total scores. There was a significant correlation between Factor 1 (ability to identify emotions) scores and both HDRS scores (Spearman Rho¼ 0.3180, p ¼ .0141) and HARS scores (Spearman Rho ¼ 0.3047, p ¼ .02) and a trend for significance Table 16.1 Background Characteristics Variable Age [Mean (SD)] Sex (% of females) Years of education [Mean (SD)] Socioeconomic status (% of Classes IV and V) Employment (% of unemployed) Glasgow Coma Scale (GCS) [Mean (SD)] Abbreviated Injury Scale (AIS) [Mean (SD)] Functional Independence Measure (FIM) [Mean (SD)] Social Functioning Examination (SFE) [Mean (SD)]
Alexithymia (n ¼17)
No Alexithymia (n ¼ 57)
35.3 (14.5) 35.3 12.3 (3.2) 37.5
37.9 (16.6) 41.1 13.2 (2.5) 44
11.8 11.1 (3.5) 18.1 (8.5) 62.1 (9.7)
12.9 11.7 (2.8) 16.5 (8.2) 63.5 (8.3)
170 (16.9)
166 (13.7)
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Table 16.2 Psychiatric Assessment Variable
Alexithymia (n ¼ 17)
No Alexithymia (n¼ 57)
Mood disorder with major depression features (%)
40
22.5
Anxiety disorder with generalized anxiety features (%)
41.1
24.6
Alcohol abuse or dependence (%) * Fisher Exact Test, p = .0225
64.7
35.3
Drug abuse or dependence (%) * Fisher Exact Test, p = .027
41.2
15.8
Aggressive behavior (%) * Fisher Exact Test, p = .017
58.8
28.1
HAMD-17 scores [Mean (SD)]
11.9 (9.1)
8.1 (5.3)
HAMA scores [Mean (SD)]
11.8 (7.2)
10.1 (6.0)
Previous psychiatric history (%)
41.1
24.6
in the case of HDRS scores and Total TAS-20 scores (Spearman Rho ¼ 0.2341, p ¼ .0743). The rest of the correlations were not significant. We also examined the relationship between alexithymia and neuropsychological performance in memory and executive functioning tests (see Table 16.3). Accounting for the fact that educational level as well as depression and anxiety
Table 16.3 Neuropsychological Variables Alexithymia (n ¼ 12)
No Alexithymia (n ¼ 57)
7.9 (3.4)
9.5 (3.1)
Rey Complex Figure Test (Delay recall) [Mean (SD)]
14.7 (4.3)
16.7 (5.6)
Control Oral Word Association Test (Total Score) [Mean (SD)]
36.9 (15.2)
40.0 (10.4)
Wisconsin Card Sorting Test (Number of perseverative errors) [Mean (SD)]
11.0 (5.8)
8.7 (5.6)
Trail Making Test (Time B) [Mean (SD)]
74.8 (27.9)
82.8 (48.0)
Stroop Test (Color/word interference) [Mean (SD)]
37.7 (10.6)
35.8 (10.9)
Mini Mental Status Examination (Total Score) [Mean (SD)]
27.8 (1.5)
27.4 (2.3)
Variable Rey Auditory Verbal Learning Test (Delay recall) [Mean (SD)]
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might have influenced neuropsychological scores, we included these variables as covariates in the analysis of differences between the groups. Overall, we did not find significant differences between the Alex and No-Alex groups on any of the different neuropsychological measures assessing memory and executive functioning. Furthermore, neuropsychological scores were not significantly correlated with total or factor-specific TAS-20 scores. We finally examined the relationship between alexithymia and neuroimaging findings. With regard to the initial radiological findings (those obtained immediately after TBI in clinical settings), there were no significant differences between the Alex and the No-Alex groups in the frequency of focal and diffuse patterns of injury, the frequency of focal identifiable lesions in the right or left hemisphere, or in the frequency of identifiable frontal, temporal, or parietal lesions. The limited number of alexithymic patients with available volumetric MRIs (n ¼ 6) precluded group analysis of research imaging data. Multiple regression analysis, however, was performed in the whole group of patients in whom we obtained a research MRI and had TAS-20 scores (n ¼ 31). We built a multiple regression model using the total TAS-20 score as the dependent variable and the volume of the different regions of the ACC (McCormick et al., 2006), gender and GCS scores as independent variables. After adjusting for GCS, women presented lower alexithymia scores than men (F (1, 27) ¼ 5.8, p ¼ .02) and there was a statistical trend indicating that larger right dorsal cingulate cortex volume is associated with lower alexithymia scores (F(1,27) ¼ 3.8, p ¼ 0.06) (see Figure 16.1).
Estimated Alexithymia Total Score
Estimated alexithymia total score as a function of the right dorsal cingulated volume after adjusting for GCS scores in females and males 65 Male Female
60
55
50
45
3
5
7
9
1
3
5
7
4.
4.
4.
5.
5.
5.
5.
1
4.
9
4.
7
3.
5
3.
3
3.
1
3.
9
3.
7
2.
3
5
2.
2.
2.
2.
1
40 Right dorsal cingulate volume (cc)
Figure 16.1 Relationship between alexithymia and dorsal anterior cingulate cortex volumes. GCS, Glasgow Coma Scale.
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Comment In summary, when compared with nonalexithymic TBI patients, TBI patients with alexithymia had significantly higher frequency of alcohol and drug misuse, as well as evidence of impulsive aggressive behavior. Difficulty in identifying emotions (TAS-20 Factor 1) was positively correlated with measures of the severity of depressive and anxiety symptoms and with aggression scores. In addition, there was some indication that alexithymia was related to reduced volumes of the right dorsal ACC. On the other hand, we did not observe an association between alexithymia and the severity of TBI, the presence of focal lesions of the right hemisphere, or the presence of focal lesions of the frontal lobes. Furthermore, there was no association between alexithymia and executive dysfunction as measured by usual neuropsychological tests. An association between alexithymia, substance misuse, impulsivity, and aggression has been previously reported in previous studies of patients with addictive disorders (Evren & Evren, 2005; Evren et al., 2008; Loas, Otmani, Lecercle, & Jouvent, 2000; Speranza et al., 2004). We have also reported that there is significant overlap between mood disorders, alcohol misuse, and aggression among TBI patients during the first year following trauma (Jorge et al., 2004; Jorge et al., 2005). These findings should be interpreted from the perspective of the known deregulation of emotional processing resulting from prefrontal dysfunction associated with TBI. Mood disorders may result from deactivation of more lateral and dorsal frontal cortex and increased activation in ventral limbic and paralimbic structures including the amygdala (Drevets, 1999; Mayberg et al., 1997; Mayberg et al., 1999). It is in this context of increased psychological distress and negative emotional arousal that coexistent alexithymic features would further contribute to impulsive behavior and aggression. Of course, alexithymia may be associated with multiple factors, including those related to previous emotional and personality development, personal history of addictive disorders, as well as structural and functional abnormalities of medial regions of the prefrontal cortex resulting from the TBI.
Final Remarks Awareness of affective deficits among brain-injured patients has not been extensively studied. There is still controversy about the conceptualization of this clinical phenomenon and, more importantly, about the methods by which emotional awareness may be reliably assessed in this population. For instance, probably due to its more complex administration and scoring procedures, there are few studies that have used the LEAS with brain-injured subjects. Emotional awareness is a hierarchical process that ultimately has a decisive impact on complex patterns of social interaction and personal fulfillment. It is
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Taylor, G. J., Bagby, R. M., & Parker, J. D. (2003). The 20-Item Toronto Alexithymia Scale. IV. Reliability and factorial validity in different languages and cultures. Journal of Psychosomatic Research, 55(3), 277–283. Taylor, G. J., Parker, J. D., Bagby, R. M., & Bourke, M. P. (1996). Relationships between alexithymia and psychological characteristics associated with eating disorders. Journal of Psychosomatic Research, 41(6), 561–568. Teasdale, G., & Jennett, B. (1976). Assessment and prognosis of coma after head injury. Acta Neurochirurgica (Wien), 34(1–4), 45–55. TenHouten, W. D., Hoppe, K. D., Bogen, J. E., & Walter, D. O. (1986). Alexithymia: An experimental study of cerebral commissurotomy patients and normal control subjects. American Journal of Psychiatry, 143(3), 312–316. Tucker, D. M., Watson, R. T., & Heilman, K. M. (1977). Discrimination and evocation of affectively intoned speech in patients with right parietal disease. Neurology, 27(10), 947–950. Wang, J., Rao, H., Wetmore, G. S., Furlan, P. M., Korczykowski, M., Dinges, D. F., et al. (2005). Perfusion functional MRI reveals cerebral blood flow pattern under psychological stress. Proceedings of the National Academy of Sciences USA, 102(49), 17804–17809. Weinryb, R. M., Gustavsson, J. P., Asberg, M., & Rossel, R. J. (1992). The concept of alexithymia: An empirical study using psychodynamic ratings and self-reports. Acta Psychiatrica Scandinavica, 85(2), 153–162. Williams, J. B., Gibbon, M., First, M. B., Spitzer, R. L., Davies, M., Borus, J., et al. (1992). The Structured Clinical Interview for DSM-III-R (SCID). II. Multisite test-retest reliability. Archives of General Psychiatry, 49(8), 630–636. Williams, K. R., Galas, J., Light, D., Pepper, C., Ryan, C., Kleinmann, A. E., et al. (2001). Head injury and alexithymia: Implications for family practice care. Brain Injury, 15(4), 349–356. Wittgenstein, L., & Anscombe, G. E. M. (1953). Philosophical investigations: The German text, with a revised English translation (3rd edition). Malden, MA,: Blackwell. Wood, R. L., & Williams, C. (2007). Neuropsychological correlates of organic alexithymia. Journal of the International Neuropsychological Society, 13(3), 471–479. Yamasaki, H., LaBar, K. S., & McCarthy, G. (2002). Dissociable prefrontal brain systems for attention and emotion. Proceedings of the National Academy of Sciences USA, 99(17), 11447–11451. Yehuda, R., Steiner, A., Kahana, B., Binder-Brynes, K., Southwick, S. M., Zemelman, S., et al. (1997). Alexithymia in Holocaust survivors with and without PTSD. Journal of Traumatic Stress, 10(1), 93–100.
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Anosognosia and Hysteria
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Neuroanatomy of Impaired Body Awareness in Anosognosia and Hysteria: A Multicomponent Account Roland Vocat and Patrik Vuilleumier
What is more disconcerting than someone who cannot move his arm and/or leg but is unaware of this deficit? Or someone who can move and walk normally but is nevertheless convinced of being paralyzed? How would it be possible to remain ignorant of one’s own body state? These questions have puzzled physicians and neurologists for more than a hundred years, and still remain a matter of debate. Both of these perplexing conditions have been commonly observed in medical practice for many centuries, and they are still frequent nowadays, respectively called anosognosia and hysterical conversion in our modern clinical terminology. Yet the underlying mental and physiological mechanisms of such impairments in bodily awareness are far from being understood. The phenomenon of anosognosia occurs in patients with cerebral injuries such as stroke, most often involving the right hemisphere. In this condition, a severe neurological deficit, like hemianopia or hemiplegia, is not recognized by the patient, even after direct confrontation. The most common manifestation of anosognosia is anosognosia for hemiplegia (AHP), in spite of the fact that paralysis can be easily demonstrated to the patient and has profound consequences for his or her everyday life. However, anosognosia can affect other neurological domains, such as memory, blindness, aphasia, and so forth (see other chapters in this volume). Since the original description by Babinski (1914), it is well recognized that this neuropsychological syndrome cannot be simply explained by a general cognitive decline or dementia, but results from specific losses in sensorimotor awareness. By contrast, hysterical conversion is in many ways a mirror condition, in which the patients experience a deficit of motor, sensory, or cognitive functions 359
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without any organic neurological damage, and without intentionally feigning it. Like anosognosia, patients with hysterical conversion frequently present with a weakness or paralysis of one or several limbs, but other common deficits may involve memory, vision, or language disturbances. This phenomenon was extensively studied by pioneer neurologists in the nineteenth century, including Babinski himself (Babinski & Dagnan-Bouveret, 1912) and his master Charcot (1892), but it then became essentially attributed to unconscious psychiatric factors following the work of Janet (1887, 1889, 1911) and Freud (Freud & Breuer, 1895). In this chapter, we will review recent studies that investigated these two conditions using neuropsychological measures, as well as structural and functional brain imaging techniques. We will first describe data concerning anosognosia and then turn to hysterical conversion. Finally, we will consider whether similar mechanisms might be involved in both cases, and we will highlight the notion that distinct neural pathways are likely to contribute to different distortions of awareness for one’s own bodily state.
Anosognosia for Hemiplegia Anosognosia for hemiplegia (AHP) involves a failure to acknowledge a paralysis after brain damage (see Bottini et al., Chapter 2; Kranath & Baier, Chapter 3; and Heilman & Harciarek, Chapter 5, this volume), but the clinical manifestation of this phenomenon may take many different forms. Indeed, one of the most typical features of anosognosia is certainly its variability. It is likely that different types or different components of AHP might exist and show various expressions in different patients (see Marcel, Tegner, & NimmoSmith, 2004; for a review, see Vuilleumier, 2004). First of all, anosognosia is often fluctuating in time. Patients may answer the same question about a particular function differently at different moments. Secondly, a lack of explicit report of the deficit is sometimes associated with discrepant remarks (e.g., ‘‘My arm is tired today’’) or behaviors (e.g., accepting to stay in bed) that suggest the existence of some acceptance or some implicit knowledge of the deficit. Thirdly, the default in awareness may concern different aspects of a deficit: its presence or its nature (e.g., ‘‘No, I am not paralyzed’’), its cause (e.g., ‘‘I am in the hospital because I got a cold’’), its consequences for a particular action (e.g., ‘‘my arm is weak but I am able to open this bottle’’), or for the patient’s everyday life (e.g. ‘‘I have to go back home because next Monday I have to go to work’’), as well as the necessary adjustments (e.g. ‘‘At home, I will be able to dress and take a shower on my own’’). These different domains are usually not affected at the same level. Finally, different deficits in the same patient can show different levels of awareness. Thus, anosognosia may be selective for a particular modality (e.g., a patient is anosognosic for his hemianopia but not his plegia or vice
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versa) and sometimes even more selective in a given modality (e.g., a patient is anosognosic for the plegia of his arm but not his leg). These multiple manifestations of anosognosia make its characterization and measurement difficult. No standard comprehensive scale has been developed to take into account this whole complexity. Hence, anosognosia is often estimated along one particular dimension only, such as the severity of unawareness in relation to varying degrees of confrontation with the deficit (direct or indirect). For hemiplegia, the most commonly used scale is the four-level questionnaire developed by Bisiach, Perani, Vallar, and Berti (1986), which probes for an explicit verbal acknowledgment of the motor impairment. This scale grades the severity of AHP as a function of whether plegia is reported after a general question about health, after a specific question about the arm, after a motor confrontation or if it is not reported. Other questionnaires (Cutting, 1978; Feinberg, Roane, & Ali, 2000) also assess the existence of related phenomena such as somesthesic illusions or somatoparaphrenias, but in a purely descriptive and itemized manner rather than according to a systematic classification scheme (for review of assessment methods, see Orfei et al., 2007; Vuilleumier, 2000).
Frequency and Evolution Anosognosia for hemiplegia is essentially an acute phenomenon that most often disappears within a few weeks after acute brain injury. A meta-analysis by Baier and Karnath (2005) noted that it was found in 10%–18% of stroke patients with hemiparesis. In a recent study conducted by our group (Vocat et al., in preparation), we found that among 58 right-hemispheric strokes with hemiplegia, onethird were associated with unawareness of the motor deficit when patients were examined 3 days after the stroke. One week post-stroke, one-fifth of the patients were still anosognosics, while this number decreased to 5% half a year later (see Figure 17.1). Hence, only in rare cases, anosognosia may persist beyond the acute phase and even become chronic. In our study, we also asked patients to describe their awareness for the onset of their symptoms and their emotional reaction at this time. Answers to this question revealed that even some patients who were nosognosic 3 days after stroke during our examination could not report precisely nor lateralize their symptoms at onset, or showed an inappropriate emotional reaction. Thus, at this very early stage (a few hours after the stroke), two-thirds of the patients could presumably be classified as anosognosic. Moreover, this percentage is certainly underestimated, as patients had the opportunity to modify their initial memory according to the report of doctors or relatives. These observations suggest that anosognosia may not be an extraordinary state in such conditions, but a rather ‘‘normal’’ or at least typical phase following sudden neurological change (especially when involving certain areas in the right hemisphere). After acute insults such as a stroke, the brain probably needs sufficient time and new information to
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Nosognosics
Anosognosics
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
Onset
3 days
1 week
6 months
Figure 17.1 Evolution of awareness for motor deficits over time in our prospective study. The proportion of patients with/without AHP is shown for the day of stroke and then 3 days later, one week later, and 6 months later (n ¼ 50, 50, 44 and 19 patients, respectively). Anosognosia at stroke onset is separated in two groups, reflecting either nosognosia or anosognosia, as estimated by the report from the patient (3 days poststroke) concerning the installation of his neurological symptoms. For the three other periods, anosognosia was estimated according to the standard procedure of the Bisiach questionnaire (patients were considered as anosognosics with a Bisiach of 2 and 3 and nosognosics with a Bisiach of 0 and 1, as suggested by Baier & Karnath (2005)). The timecourse indicates that anosognosia is essentially an acute phenomenon, concerning 2/3 of the patients at the stroke onset, but rapidly decreasing to 1/3 only three days later, and 1/5 one week later. After 6 months, severe anosognosia persists in a few rare cases.
adjust and reorganize itself. This period may therefore be particularly propitious for the emergence of anosognosia, while some unkown factors or specific deficits might lead to its persistence and cause related behavioral manifestations seen beyond the very acute stage. The consequences of anosognosia can be dramatic because it sometimes prevents the patients from looking for necessary treatments (or may delay emergency care such as thrombolysis). When these patients live alone at home, they can spend hours or days on the floor, without feeling the need to call for help or realizing the reason of their fall. Moreover, their anosognosia may even engender more danger and injury due to the patients trying to stand up and walk. Once hospitalized, another harmful consequence is the lack of participation in therapy (see Maeshima et al., 1997). As the patients believe that everything is fine, they sometimes see no utility to stay in the hospital and to participate in therapies (from drug treatment to physical therapy). Finally, a more general outcome of
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anosognosia is a lack of concern for new adjustments concerning their everyday life (work, family, house, etc.). Patients sometimes want to go on with their work and past activities, at the despair of their relatives. These unrealistic goals may even persist when patients appear more aware of the existence of physical deficits. Moreover, some patients may acknowledge their deficit but show no particular concern for it (anosodiaphoria). The social impact of these behaviors is also very important. All these consequences constitute well-known limitations for the treatment and recovery of stroke (Ownsworth & Clare, 2006; Ownsworth et al., 2007; Ownsworth & McKenna, 2004). Hence, a better understanding of the mechanisms of anosognosia and their clinical evolution are critical in order to act effectively upon them, so as to improve the management and rehabilitation of these patients.
Mechanisms and Comorbidity Since the original description of AHP by Babinski (1914), more than 100 years of clinical research have highlighted both the regularities and oddities of this deficit, and several researchers have proposed a possible explanatory theory, yet there is still very little agreement on the exact neuropsychological mechanisms involved nor on their cerebral substrates. In fact, most of the existing theories have been counterattacked by clinical observations or inconsistencies arguing against them. Many of the first attempts to understand anosognosia focused on the identification of a single cause for this phenomenon (see Table 17.1). Thus, among the most influential proposals, researchers have pointed to the possible role of a deficit in sensation or proprioception (Babinski, 1914), visuospatial neglect (Bisiach, Vallar, Perani, Papagno, & Berti, 1986), confabulations (Feinberg, 1997), memory impairments (Starkstein, Fedoroff, Price, Leiguarda, & Robinson, 1992), overestimation of self-performance and lack
Table 17.1 Summary of Classic Hypotheses on Anosognosia for Hemiplegia Babinski (1914): sensory and/or proprioceptive feedback Weinstein & Kahn (1955): denial and personality traits (e.g., perfectionism) Bisiach et al. (1986): spatial or personal neglect/dyschiria McGlynn & Schachter (1989): access to a specific conscious awareness system Levine (1990): discovery theory (proprioception and cognitive impairment) Heilman (1991): feedforward theory (motor initiation and preparation) Starkstein et al. (1992): mental flexibility and memory abilities Feinberg (1997): neglect and confabulation Frith et al. (2000): deficit in comparing planned and executed action Marcel et al. (2004): overestimation of self-performance and lack of mental flexibility Vuilleumier (2004): ABC model (deficits in appreciation, beliefs, and checks) Davies et al. (2005): two-factor theory (two deficits preventing the discovery)
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of mental flexibility (Marcel et al., 2004), psychological defense mechanisms (Weinstein & Kahn, 1955), a default in the intentional planning of movement (Heilman, 1991), a failure to compare planned and executed action (Frith, Blakemore, & Wolpert, 2000; Vallar & Ronchi, 2006), or a disruption and/or disconnection of a specific module dedicated to motor awareness (McGlynn & Schacter, 1989). However, none of these proposals has been found to be sufficient, by itself alone, to account for all the complex features of anosognosia. Hence, more recent models have proposed that AHP might result from a combination of different deficits, rather than from a single ‘‘core’’ deficit. For example, Levine proposed an interesting ‘‘discovery theory’’ (Levine, 1990), according to which anosognosia would appear when a deficit of proprioception or perception from a body part co-occurs with a global cognitive dysfunction that prevents a correct ‘‘inference’’ of the lack of function. A similar idea was proposed as an ‘‘ABC’’ model (Vuilleumier, 2004), where awareness relies on a set of neuropsychological functions mediating Appreciation, Belief, and Check processes. Thus, anosognosia might emerge due to various deficits affecting appreciation (due to different possible combinations of neurological and neuropsychological losses) together with deficits in other cognitive or affective functions necessary to change one’s own beliefs and/or act upon signals of uncertainty. Importantly, in this perspective, anosognosia might represent a similar clinical endpoint caused by a constellation of distinct deficits, each of which having a different severity in different patients, but adding up to produce the same total effect. Likewise, more recently, Davies, Davies, and Coltheart (2005) proposed explicitly for the first time that anosognosia might emerge because of different ‘‘cocktails’’ of deficit. Thus, their two-factor theory asserts that a combination between a neuropsychological deficit (the first factor) along with a more general cognitive impairment (the second factor) can be sufficient to produce anosognosia. Nevertheless, the exact combination of factors necessary to produce AHP has not been directly demonstrated yet. We recently conducted a large prospective study (Vocat et al., in preparation) in which we systematically looked at the neurological, neuropsychological, and psychological components associated with AHP, in a population of patients with a first acute right-hemisphere stroke. Among a series of 337 patients, 58 were recruited because of a significant unilateral motor weakness. Our assessment was made at three different time points: 3 days after stroke (hyperacute stage), 1 week later (post-acute stage), and 6 months later (chronic stage). Besides an assessment of AHP using the Bisiach scale (Bisiach, Vallar, Perani, Papagno, & Berti, 1986) and Feinberg questionnaire (Feinberg, Roane, & Ali, 2000), we tested for a wide range of neurological functions, including motor strength, sensation, proprioception, vision, and vigilance, as well as several neuropsychological domains such as perceptual and motor neglect, executive functions,
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memory, orientation, global cognitive functioning, and self-evaluation of both motor and cognitive tasks (Marcel et al., 2004), plus psychological variables such as mood, anxiety, irritability, and optimism. To take into account the different degrees of AHP and its fluctuations over time, we computed a single score of anosognosia based on the mean from two different evaluations on the Bisiach scale plus the Feinberg questionnaire (separated by intervening tests), for each of the assessments. Our results (Vocat et al., in preparation) showed that, for the first two periods (at 3 days and 1 week), almost all neurological and neuropsychological tests were related to the severity of anosognosia. Hemianesthesia, impaired proprioception, reduced vigilance, hemianopia, visual and tactile extinction, spatiotemporal disorientation, visuospatial neglect, and poor anterograde memory were all found to show significant correlations with AHP. This pattern of data is consistent with the notion of a multifactorial disorder and the role of large brain lesions that are likely to disrupt several cognitive functions. There was no reliable correlation with the severity of motor weakness, or with ‘‘simple’’ frontal functions. A stepwise multiple regression analysis indicated that the degree of proprioceptive loss and extrapersonal spatial neglect were the strongest predictors of the severity of AHP. However, despite the frequent associations of some deficits, we could find several patients who showed a dissociation between the same deficits, including three who had AHP with severe neglect but no proprioceptive loss or vice versa, supporting the idea that AHP is not related to a unique set of deficits, but rather results from the sum of combined impairments whose relative severity may vary across patients (Vuilleumier, 2004). Notably, our psychological testing (which attempts to assess depression, anxiety, anger, interest, optimism, etc.) failed to reveal any systematic association with AHP, for any of the testing periods. This result does not support the notion that premorbid personality factors or secondary affective reactions play a major role in the emergence of AHP. Finally, we also examined the evolution over time of the different deficits, in relation to the evolution of AHP. We observed that anosognosia showed the same time course with a rapid decrease as the deficit of proprioception, visuospatial neglect, and temporospatial disorientation, between the hyperacute (3 days) and post-acute (1 week) stages. But at the final testing stage, 6 months after the stroke, only neuropsychological components were still linked with anosognosia, in particular visuospatial neglect, memory impairment, and temporospatial disorientation. Taken together, these results suggest that even if different combinations of neurological and neuropsychological deficits can be responsible for AHP, they may have a different impact on its persistence beyond the acute stage. While both neurological and neuropsychological impairments are involved in the emergence of AHP, the neuropsychological factors seem more determinant for chronic persistence.
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Neuroanatomical Substrates To understand the possible mechanisms underlying AHP, many researchers have tried to identify specific neuroanatomical correlates. Of course, such an approach necessarily implies that this syndrome is not purely due to some reactive psychological defense mechanisms, but represents a direct clinical manifestation of dysfunction in one or several brain regions. In accord with this assumption, a first major anatomical characteristic of AHP is the hemispheric asymmetry that has been reported since the earliest descriptions of this phenomenon and has been subsequently observed by many investigators (see Heilman & Harciarek, Chapter 5, this volume). A greater frequency of both anosognosia and anosodiaphoria after right hemispheric stroke was already emphasized by Babinski himself (1914). More recently, experimental studies (Adair, Gilmore, Fennell, Gold, & Heilman, 1995; Breier et al., 1995; Gilmore, Heilman, Schmidt, Fennell, & Quisling, 1992; Lu et al., 1997; Lu et al., 2000) have used the Wada procedure in epileptic patients (i.e., injecting anesthetics such as amytal in one or the other hemisphere for presurgical testing of language laterality) and could thus confirm a relative dominance of the right hemisphere in the production of AHP during transient hemiplegia. In these studies, the limitations of testing due to language deficits after left hemispheric dysfunction could be overcome by preparing the patients before the injection of amytal so that they could expect the deficit and know how to communicate (via a nonverbal means) during the Wada test. This procedure allowed researchers to probe whether patients could acknowledge their paralysis, and also to obtain a verbal report following the complete remission of symptoms after the Wada test. The occurrence of AHP during the Wada test clearly demonstrates that a psychodynamic explanation of AHP is not sufficient, since patients know in advance about the temporary existence and provoked nature of their plegia but still deny it upon direct assessment. Note however that even if this hemispheric asymmetry is well established, AHP can also be occasionally observed with left hemispheric lesions. Moreover, anosognosia of language disorders is frequently seen in patients with Wernicke’s aphasia, which typically follows lesions in the left hemisphere (see Kertesz, Chapter 6; Cocchini & Della Sala, Chapter 7, this volume). These findings point to the fact that anosognosia, as a general phenomenon affecting different domains, does not relate to a single module located in a particular cerebral region that would be responsible for a generic knowledge about one’s current health; but it can emerge after damage to distinct cognitive domains involving different lesion sites. Therefore, the hemispheric asymmetry usually described in anosognosia is undoubtedly dependent on the specific neurological function that is concerned (e.g., hemiplegia versus language deficits). Another more general observation is that anosognosia usually occurs after large brain lesions (Feinberg, Haber, & Leeds, 1990; Hier, Mondlock, &
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Caplan, 1983; Levine, Calvanio, & Rinn, 1991; Willanger, Danielsen, & Ankerhus, 1981). Nevertheless, some cases have been reported with a relatively focal lesion (Bisiach et al., 1986; House & Hodges, 1988). However, a variety of different brain areas have been held to be critically implicated, including the temporoparietal cortex, thalamus, basal ganglia, as well as their interconnecting pathways in the posterior deep white matter (for review, see Vuilleumier, 2000). A few case reports have also described the occurrence of AHP with intriguing noncortical lesions, involving, for example, the pons (Assenova, Benecib, & Logak, 2006; Bakchine, Crassard, & Seilhan, 1997; Evyapan & Kumral, 1999), together with some preexisting cognitive decline reported in some of these patients only (Bakchine et al., 1997). A disruption between frontal and parietal areas due to ‘‘diaschisis’’ has been suggested to explain these phenomena. A more systematic investigation of lesions associated with AHP was recently conducted by using different types of statistical overlap analysis (see Bottini et al., Chapter 2, and Karnath & Baier, Chapter 3, this volume). Karnath et al. (Baier & Karnath, 2008; Karnath, Baier, & Nagele, 2005) suggested a key role for damage to the posterior insula, whereas Berti et al. (2005) found maximal overlap in premotor, motor, and sensory cortical areas. In addition, among two recent meta-analyses of previous anatomical studies, one pointed to the combination of parietal and frontal lesions and their possible impact on corticosubcortical circuits underlying awareness of motor acts (Pia, Neppi-Modona, Ricci, & Berti, 2004), whereas another (Orfei et al., 2007) underscored a predominant involvement of the prefrontal and parieto-temporal cortex, as well as of the insula and thalamus (see also Vuilleumier, 2000). However, these overlap studies present with a few methodological issues that may limit their interpretation. In particular, these techniques require a dichotomic classification separating the patients in two groups: anosognosics versus nosognosics. But from a clinical perspective, this cut-off does not reflect the multiple variations and fluctuations of anosognosia. Moreover, some patients may receive the same total score of anosognosia on Bisiach or Feinberg questionnaire, but have different combinations of causal deficits (as predicted by the ABC model, see above; Vuilleumier, 2004). Furthermore, patients with acute and more chronic forms of anosognosia are sometimes mixed in some studies. To remedy some of these problems, in our own recent study of right-hemisphere stroke patients (Vocat et al., in preparation), we performed an overlap analysis of lesions that took into account the different degrees of anosognosia in different patients, as well as its evolution over time. We reconstructed the lesions for each of our patients on the basis of the cerebral scanner made 1 week after the stroke, in a blind manner. To analyze statistically the sites of maximal overlap, we applied a voxel-by-voxel lesion symptom mapping (VLSM) method as described elsewhere (Bates et al., 2003; Grandjean, Sander, Lucas, Scherer, & Vuilleumier, 2008), which allows taking into account the severity of
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anosognosia in different patients, by weighing the importance of each lesion by the mean score on Bisiach and Feinberg scales (calculated from the two successive assessments). Thus, this method highlights those voxels whose damage leads to the most severe cases of AHP. In the hyperacute phase (3 days post stroke), the most common areas of damage in patients with a severe left AHP (relative to those without or with milder AHP) were found in the anterior insula, plus the anterior part of the claustrum and putamen, anterior internal capsule, head of caudate, and anterior paraventricular white matter within the right hemisphere (see Figure 17.2A). For patients with persisting AHP in the second phase 1 week later, several other regions of the right hemisphere were also selectively affected, now including the premotor cortex, temporo-parietal junction, frontal white matter in anterior internal capsule, as well as the hippocampus, and amygdala (see Figure 17.2B). Thus, while lesions in anterior insula and anterior subcortical structures were most distinctive for AHP in the hyperacute period (3 days after stroke), additional lesions in parietal, frontal, and/or temporal structures were needed to
Figure 17.2 Results of statistical anatomical lesion analysis in our prospective study of AHP. Voxelwise mapping of brain areas correlating with anosognosia scores in the hyperacute phase (A: 3 days after stroke) and in the post-acute phase (B: 1 week after stroke). The voxels highlighted are those that show a significant difference (p < .01) in the severity of anosognosia between patients with/without a lesion in these voxels. (See Color Plate 17.2)
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produce a more sustained AHP (1 week later). Taken together, these anatomical data do not only converge with the notion that AHP is likely to result from multiple component deficits but also point to several possible mechanisms underlying these deficits such as those entailing impairments in appreciation, belief, and check processes. On the one hand, our findings in hyperacute stage (3 days after stroke) converge with the report of frequent insula damage by Karnath & Baier (Chapter 3, this volume). The insula might be involved in feelings of body ownership and agency (Karnath, Baier, & Nagele, 2005), but its anterior sector is also implicated in error monitoring (Magno, Foxe, Molholm, Robertson, & Garavan, 2006; Taylor, Stern, & Gehring, 2007), in representing internal body states (Critchley, Wiens, Rotshtein, Ohman, & Dolan, 2004), and in processing uncertainty, in concert with prefrontal cortices and basal ganglia (Harris, Sheth, & Cohen, 2008). The latter structure also plays a key role in performance monitoring and behavioral adjustments (Ullsperger & von Cramon, 2006) and was also more frequently damaged in our patients with AHP, together with white-matter connections in subcortical frontal regions. Damage to these circuits may therefore disrupt the neural systems normally responsible for the monitoring of motor actions and errors (and for implementing a subsequent ‘‘switch’’ in behavior). On the other hand, our findings in the post-acute stage (1 week after stroke) converge with those of Berti et al. (2005), suggesting a crucial role for lesions in premotor cortex. Premotor areas do not only mediate motor initiation and preparation but are also thought to be responsible for generating a corollary discharge that can be used to monitor and adjust movements, according to sensory and proprioceptive feedback (see the feedforward model of action control proposed by Blakemore, Wolpert, & Frith, 2002). Accordingly, a recent study of Fotopoulou et al. (2008), in which a rubber hand was used to simulate movement of the left paralyzed arm, showed that anosognosic patients can accurately discriminate between the presence/absence of movement of the rubber hand, as long as they are not instructed to imagine themselves doing this movement. When a motor intention is generated (by having to imagine to move), a movement of the rubber hand is incorrectly reported even if it was motionless. This intriguing study shows the importance of motor intention and preparation in the anosognosic phenomenon, which can dominate actual sensory information. However, such findings are not readily compatible with other observations, suggesting that a lack of motor intention might play a causal role in abolishing motor awareness in anosognosia (Gold, Adair, Jacobs, & Heilman, 1994; see also Heilman & Harciarek, Chapter 5, this volume). We also found that other brain regions were important in the maintenance of anosognosia during the post-acute phase (1 week after stroke), including the temporo-parietal junction (TPJ) and the amygdalo-hippocampal complex. Numerous studies have shown that the right TPJ is critically linked to spatial attention (see Halligan, Fink, Marshall, & Vallar, 2003, for a recent review),
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and damage to this region typically produces left hemispatial neglect (Mort et al., 2003). In keeping with this, neglect has often been suspected to play an important role in AHP (Bisiach et al., 1986; Cutting, 1978; Hier, Mondlock, & Caplan, 1983; Starkstein, Fedoroff, Price, Leiguarda, & Robinson, 1992; Vuilleumier, 2000), and our own study also revealed that extrapersonal neglect was one of the major neuropsychological disorders correlating with both the severity and time-course of AHP (Vocat et al., in preparation). Finally, a less expected finding was the correlation of AHP with damage to the amygdalo-hippocampal complex in medial temporal lobe. These regions are known to play a key role in memory and emotion. The hippocampus subserves the encoding of events in episodic memory (Squire, 1992), and lesions in this area prevent any integration of new information into current knowledge. The amygdala is a structure critically implicated in emotional processing and learning (see Phelps & LeDoux, 2005, for a review), with a particular importance for fear (Ohman & Mineka, 2001) and, more generally, for the detection and appraisal of self-relevant stimuli (Sander, Grafman, & Zalla, 2003). Thus, lesions to this structure may cause a loss of fear responses (Adolphs et al., 2005) as well as an incapacity to take into account various forms of feedback that are relevant for subsequent behavioral adjustments (Ousdal et al., 2008). In the case of anosognosia, it is tempting to speculate that damage of these two structures could lead to more superficial processing of the abnormal or threatening feedback generated by a paralyzed limb and motor failures, as well as to greater forgetfulness of these events. Consistent with this hypothesis, our results (Vocat et al., in preparation) also indicated a mild but significant correlation between memory difficulties and anosognosia in the post-acute (1 week) and chronic (6 months) phases. To sum up, our results help reconcile the apparent discrepancies between previous studies on the neural bases of anosognosia (Berti et al., 2005; Bisiach et al., 1986; Karnath et al., 2005). We show that no single brain area seems to be sufficient by itself to produce AHP. Indeed, no single brain area appears to be damaged in 100% of anosognosic patients. Rather, a complex network of interacting cerebral regions seems likely to be implicated in the occurrence and persistence of this syndrome. The critical lesions might also act by disconnecting white-matter pathways between subcortical and posterior brain regions to more anterior areas in the frontal lobe. This widespread network appears to encompass not only proprioception and spatial attention but also motor planning, action monitoring, memory, and affective relevance detection. Each of these functions might potentially be affected in AHP, but perhaps to different degrees in different patients.
A Multicomponent and Multifocal Disorder Both the neuropsychological and anatomical analyses reviewed above clearly converge to indicate that AHP is likely to represent a multicomponent syndrome,
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associated with multifocal brain damage as typically seen in large stroke lesions. Different combinations of deficits might add up to produce similar behavioral outcome or interact together to produce different forms of AHP. Thus, consistent with our ABC hypothesis (Vuilleumier, 2004), a severe impairment in one or many of the ‘‘appreciation’’ components (such as proprioception and spatial attention) might be sufficient to cause AHP in the presence of mild impairments in the ‘‘check’’ components (such as action monitoring or affective appraisal). But conversely, in another case, AHP might primarily arise due to a severe disruption of check components despite minor losses in proprioception and a lack of neglect. This ABC combinatorial rule would be consistent with occasional observations of striking dissociations between AHP and some deficits that are otherwise known to be strongly correlated with AHP (e.g., spatial neglect). However, the exact cognitive processes underlying each of the ABC components and their neuroanatomical correlates still remain to be better characterized. Further studies are needed to test a range of abilities associated not only with sensory and motor functions but also related to reasoning, belief formation, error monitoring, affective processing, and so forth. Below we speculate on a few specific dimensions of self-awareness and self-monitoring that might potentially offer valuable avenues for future investigations of AHP.
Evidence for a Multiple Parallel System Account Which combination of neurological and/or neuropsychological deficit is crucial to produce anosognosia is still unknown. As noted above, it is possible that several different factors are involved, and that a particular ‘‘cocktail’’ of deficits is necessary to explain the emergence and/or the persistence of anosognosia after brain damage, consistent with our results showing the co-existence of multiple cognitive and anatomical correlates. In addition, different forms or different degrees of anosognosia might exist and reflect different components in the syndrome. Here we briefly review a number of cognitive and affective processes that have been identified in other neuropsychological disorders as well as during normal performance in healthy subjects and that might potentially play some role in the behavioral manifestations of anosognosia.
Implicit and Explicit Processing Clinical observations suggest that there are essentially four types of possible reactions when confronted with a neurological deficit such as plegia after cerebral injury. The first case is a full awareness of the deficit. Patients can describe their deficit and the handicap that will affect their life. A second case is a superficial description of the symptom (usually with some minimization of its impact), but the patients fail to take their condition into account when
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projecting themselves in the future or when making decisions. This corresponds to the notion of anosodiaphoria (i.e., a lack of affective concern for the deficit with a preserved sensory and cognitive appreciation), and it accords with the frequent disorders seen in patients with traumatic brain injury (TBI), typically attributed to frontal lobe syndrome (Levine, Dawson, Boutet, Schwartz, & Stuss, 2000; Levine et al., 1998; Prigatano & Altman, 1990). Third, patients may present with a classic and full form of anosognosia. They do not spontaneously report their deficit, deny it even after motor confrontations, behave as if they could go on with their past life without changes, and show no clear understanding of the reasons why they are currently investigated in the hospital or attribute their illness to a more abstract and causal level without direct reference to the deficit (i.e., they may acknowledge a diagnosis of stroke or heart attack but have no paralysis). Such patients may even hallucinate accurate movement with their affected limb and report that actions made on request have been correctly executed despite the lack of any visible movements, resembling a form of motor confabulation (Feinberg, 1997). However, a fourth case concerns anosognosic patients who seem to have some unconscious knowledge of their paralysis (corresponding to the notion of ‘‘dunkle Erkenntnis’’ described by Anton (1898)). These patients are compliant and stay calmly in the hospital, have compensatory movements to adjust to their paralysis, and participate in therapy without opposition, but they show no clear knowledge of what is wrong with them. After confrontations with their motor weakness, these patients may confess that they did not reach the demanded state but justify their failure by false but ‘‘plausible’’ reasons like ‘‘my arm is tired,’’ ‘‘today it doesn’t work as I want,’’ ‘‘it takes more time than usual,’’ ‘‘my arm is not paralyzed, but a little sleepy now,’’ ‘‘my arm is not sufficiently warmed up,’’ or ‘‘I don’t want to do this now’’ (and so forth). These justifications might reflect some trace of ‘‘implicit’’ detection of the deficit, at least to the point where the outcome of a specific goal is not adequately realized. Nevertheless, these patients appear unable to integrate this mismatch and new information related to their condition so as to infer the existence of their (seemingly unnoticed) deficit. Based on these observations, it would be tempting to distinguish between at least two levels or two types of ‘‘awareness of the deficit’’: namely, an implicit and an explicit aspect. Most current accounts of AHP and assessment procedures assume that these two levels lie on a continuum of severity, and therefore conflate them into a single score. However, we believe that they might reflect different aspects of sensori-motor monitoring, and that it might be useful to separate these different behavioral manifestations by using distinct measures. In keeping with this, a recent study (Nardone, Ward, Fotopoulou, & Turnbull, 2007) showed that patients with AHP showed slower reaction times to visual targets preceded by a word related to their motor deficit (arm, hand) verus another neutral body part (eye, back). Because this slowing was the most severe in the two patients with the most severe anosognosia, these authors concluded that AHP might reflect an
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active suppression mechanism. However, other mechanisms underlying a dissociation between implicit and explicit knowledge of the paralysis might potentially produce a similar pattern. Also consistent with this hypothesis, it has been reported that patients with AHP might report some knowledge of their deficit after manipulation reducing spatial neglect such as vestibular stimulation (Bisiach, Rusconi, & Vallar, 1991; Ramachandran, 1995; Rode et al., 1992; Vallar, Guariglia, & Rusconi, 1997), or are hypothesized to do so when reporting their dreams after sleeping (Ramachandran, 1996). Moreover, a number of observations suggesting a dissociation between unconscious and conscious processing have been described in other domains in neuropsychology (De Gelder, De Haan, & Heywood, 2002). In particular, in visual perception, many phenomena can reveal the existence of information processing in the absence of conscious verbal report. This may happen, for example, for stimuli in the left hemifield in patients with spatial neglect (Marshall & Halligan, 1988; Vuilleumier, Schwartz, Clarke, Husain, & Driver, 2002); or even more impressive, in patients with blindsight after visual field loss (Stoerig & Cowey, 1997). These examples show that, in conditions where perception is very incomplete and poor (due to deficit of attention or primary sensory processing), some processes in the brain may still ‘‘detect’’ sensory features that are not available to conscious report. Nevertheless, this residual subliminal processing can have indirect effects on the patient’s behavior, by influencing his or her responses or choices even without him being aware of it, as shown in neglect patients who prefer a stimulus over another based on unseen cues (Marshall & Halligan, 1988). Even in normal subjects, unconscious priming by an undetected, briefly presented stimulus can facilitate its reprocessing during a later supraliminal presentation (Dehaene et al., 2001) or produce subsequent biases in accessing its semantic field (Ortells, Daza, & Fox, 2003). Based on these observations, it is therefore possible to imagine that, in condition of altered sensori-motor feedbacks, the brain might still detect some mismatch between a planned action and its real outcome despite a lack of conscious awareness. This might exist in some patients but not all of them, resulting in different subtypes of AHP, as suggested by the clinical observations described above. However, the exact neural substrates for these effects still remain to be explored.
Action Monitoring and Error-Related Processing Neuroscience research in healthy subjects has identified a specific neurophysiological marker for the detection of any mismatch between expected and actual motor outcome. This has been studied in various paradigms investigating the EEG responses evoked by error detection, and it led to the discovery of a specific waveform after error commission, known as the error-related negativity (ERN; see Falkenstein, Hoormann, Christ, & Hohnsbein, 2000, for a review). This
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EEG component shows up 50 to 100 ms after a motor error and has neural sources located primarily in the anterior cingulate cortex (ACC; Dehaene, Posner, & Tucker, 1994; van Veen & Carter, 2002). Importantly, the very short latency of the ERN after an error suggests that it cannot simply result from processing the sensory consequences of an erroneous response. Rather, it is likely to be generated by some internal comparator mechanisms operating on a representation of the motor command or response selection itself, and thus might arise prior to conscious awareness of the error. Accordingly, elegant experiments using antisaccade tasks in normal subjects (Endrass, Reuter, & Kathmann, 2007; Nieuwenhuis, Ridderinkhof, Blom, Band, & Kok, 2001) have shown that a clear ERN can be elicited when errors are made but not verbally reported. Thus, incorrect saccades with small movements in the wrong directions did not reach consciousness but nevertheless were detected by internal monitoring processes. Similar results have been found with other paradigms such as the Stroop task (Hester, Foxe, Molholm, Shpaner, & Garavan, 2005; O’Connell et al., 2007). On the contrary, a study by Larson, Kaufman, Schmalfuss, and Perlstein (2007) reported that TBI patients were aware of errors in a Stroop task (as much as control participants) but showed a decrease in the amplitude of the ERN. However, these patients showed no difference in another error-related component, the Pe, a positive waveform that arises later (300 to 500 ms post-onset, possibly reflecting some kind of P300 component), and that is thought to reflect conscious processing of errors. Other studies also confirmed that the generation of ERN does not depend on awareness of errors. For example, Stemmer, Segalowitz, Witzke, and Schonle (2004) showed that patients with damage to the anterior cingulate cortex had a diminished ERN, but with a preserved awareness of errors. These findings suggest that regions other than ACC are important for conscious monitoring. Brain regions involved in error processing have been further established by the work of Ullsperger, von Cramon, and Muller (2002). These authors investigated three groups of patients with different lesion sites (in orbitofrontal, lateral frontal, or temporal cortex) during a speeded task and found that the lateral frontal cortex was the only region where damage abolished the ERN component. Remarkably, in almost all of these patients, the lesions also extended to the anterior insula, a region highlighted in our lesion analysis of patients with AHP (see above; Vocat et al., in preparation) and frequently activated in error monitoring tasks (Klein et al., 2007; Magno, Foxe, Molholm, Robertson, & Garavan, 2006; Taylor, Stern, & Gehring, 2007). In addition, other studies have been conducted in Parkinson’s disease patients (Stemmer, Segalowitz, Dywan, Panisset, & Melmed, 2007; but see Holroyd, Praamstra, Plat, & Coles, 2002), who are impaired at detecting their motor errors (see also Prigatano & Maier, Chapter 9, this volume) and show a reduced amplitude in the ERN. Taken together, these results clearly suggest that error detection relies on several neural pathways, related to at least two distinct levels of awareness: an implicit and
Motor Commands Psychological reaction
Comparison between expected and actual feedbacks
Acceptance/Denial
Sensory Hemianesthesia Tactile extinction ...
Proprioceptive Deficit of proprioception Kinesthetic illustions ...
Explicit system • Conscious error detection • Based on the quality of feedbacks and access to attentional and executive networks • Frontal-parietal cortices
Visual Hemianopia Visual extinction Visuo-spatial neglect Visual completion ...
Outcome Lack of feedforward signal Motor hallucinations Motor neglect ...
Good
• Unconscious error detection • Based on automatic monitoring and affective relevance of mismatch between goal and outcome • ACC, insula, basal ganglia, amygdala
Feeling
Altered
Altered
Implicit system
Check systems Evaluation of uncertainty Cognitive and affective shifting Change of beliefs
Knowing
Full Anosognosia Verbal report:Behavior:-
Partial Anosognosia Verbal report:Behavior:+
Good
Anoso diaphoria Verbal report:+ Behavior:-
Fuli Awareness Verbal report:+ Behavior:+
Beliefs systems Beliefs interpretations Episodic memory ...
Figure 17.3 A multicomponent model of anosognosia for hemiplegia. ACC, anterior cingulate cortex.
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automatic stage, with an early latency, reflected by the ERN component, which is presumably generated in the ACC but may depend on information processed in lateral prefrontal areas and possibly the anterior insula; as well as a more explicit stage, with a later latency and distinct neural generators (Vocat, Pourtois, & Vuilleumier, 2008). It remains to be determined how these neurophysiological markers of action monitoring (ERN and Pe) might relate to the behavioral manifestations of anosognosia, and whether they might correlate with differences in the level of awareness in these patients, reflecting implicit detection versus explicit verbal report of their deficits, respectively. Normally, these two monitoring systems are likely to be interconnected and integrated, but they might be differentially affected due to the cerebral lesion and the loss of internal feedbacks representations. In the following section, we briefly outline how these two parallel monitoring systems, implicit and explicit, might make distinct contributions to AHP and other related disorders (see Figure 17.3).
Motor Error Monitoring and Unawareness of Deficit Every movement begins with the generation of a motor goal and ends with a produced effect. Models of motor control (e.g., Blakemore, Wolpert, & Frith, 2002) assume that the brain computes the movement parameters needed to reach the desired state by planning and executing motor commands and then comparing an efferent copy of these commands with the actual outcome based on ongoing feedback (sensory, proprioceptive, visual), in order to allow online motor adjustments (see Bottini et al., Chapter 2, this volume). In hemiplegic patients, the motor command itself might be disrupted by the lesion, which might then suppress internal signals to other brain structures implicated in the monitoring of movement (see feedforwad theory of AHP in Heilman & Harciarek, Chapter 5, this volume). In addition, feedback information might also be reduced by sensory disturbances, including hemianesthesia and tactile extinction, as well as by proprioceptive loss, spatial neglect, visual deficits such as hemianopia and visual extinction, or even visual completion and kinesthetic illusions. Thus, information about the actual outcome of an action might be affected by more than a single deficit, and even more so by a combination of different deficits. Importantly, it is possible that such losses might affect the implicit, explicit, or both monitoring systems. Explicit awareness of motor impairment presumably arises through an integration of several channels (i.e., visual, proprioceptive, tactile, or motor signals) that carry feedback information about movements and become represented in a mental ‘‘global workspace’’ possibly mediated by a reverberant state of neurophysiological synchronization between fronto-parietal areas and other modality-specific regions (Dehaene, Changeux, Naccache, Sackur, & Sergent, 2006; Dehaene & Naccache, 2001; Dehaene, Sergent, & Changeux, 2003; Rodriguez et al., 1999; Tallon-Baudry & Bertrand, 1999). Access of information
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to these large-scale networks might result in a conscious ‘‘knowing’’ about the deficit, selective orienting of attention, verbal report, as well as appropriate goaldirected behavior. Lesions in fronto-parietal networks or their afferent input connections might (partly or totally) deprive the explicit action monitoring system from reliable feedback or feedforward signals necessary to consciously evaluate motor performance (Davies et al., 2005; Vuilleumier, 2004), consistent with the pattern of lesion we found to be associated with sustained AHP in the post-acute stage after stoke (1 week later; see earlier discussion). However, as previously noted, impaired access of sensorimotor information to conscious awareness may not necessarily prevent a parallel implicit monitoring system to detect anomalies in the current motor or sensory state. On the other hand, implicit monitoring or motor error processing might be mediated by distinct neural pathways, including not only the ACC (which is thought to produce the ERN component in EEG studies) but also other regions implicated in motor action monitoring such as the anterior insula (see Craig, Chapter 4, this volume) and basal ganglia. These brain regions might contribute to more automatic and ‘‘unconscious’’ processing of error signals, based on the comparison between expected and actual feedback for the planned movement (through motor, proprioceptive, tactile, and/or visual inputs). Activation of implicit error processing systems could result in a more diffuse ‘‘feeling’’ about the deficit, perhaps including emotional and arousal dimensions. A lesion, disconnection, or degradation affecting sensorimotor feedback to these pathways might therefore suppress any kind of implicit warning signal when an incorrect motor action occurs. Our lesion analysis (Vocat et al., in preparation) showed no lesion in ACC correlating with anosognosia, but the anterior insula and basal ganglia were found to be consistently damaged, together with the anterior white matter possibly connecting motor areas to ACC (see Figure 17.2B), for both the hyperacute (3 days) and post-acute (1 week) stages. In addition, our results also revealed that post-acute AHP correlated with damage to the amygdala and hippocampus, that is, brain structures critically implicated in the detection of affectively relevant stimuli and memory formation. Deficits in either of these components could further contribute to an inability to learn about the motor deficits, and hence to adjust behavior or awareness accordingly, despite preserved detection of sensorimotor errors during confrontation. Different degrees of disturbances along both the explicit and implicit monitoring systems might correspond to the four different clinical types of awareness disorders that are observed in patients (as summarized in Figure 17.3). When both systems are functionally intact, the patients have a ‘‘full awareness’’ of their motor performance (normal or impaired). When both systems are dysfunctional, the patients may present with total unawareness or ‘‘full anosognosia.’’ Not only can they not report their deficit even after confrontation, but they behave as if nothing is wrong and take risky behavior, such as trying to
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get up and walk despite hemiplegia. Typically, they are unable to accept the reasons for being admitted to the hospital. By contrast, when explicit monitoring is impaired but implicit monitoring is intact, the deficit might not be reported, yet patients present with indirect behavioral manifestations reflecting some unconscious knowledge or ‘‘feeling’’ of it. Although they deny the deficits, they may sometimes act appropriately, give awkward interpretations in response to confrontations to their weakness, or misattribute their failures to other illnesses. These patients will stay in their bed and accept medical exams or therapy. On the contrary, when explicit monitoring is preserved and implicit systems are damaged, a deficit can be verbally admitted (e.g. during confrontation), but because there is no other ‘‘feeling of wrongness,’’ the importance of the deficit is minimized or overlooked in more spontaneous conditions. Such patients may fail to adapt to their new conditions despite apparent nosognosia. This kind of disorder is common in TBI patients (see Langevin & Le Gall, 1999, for a review) but also occurs in stroke patients, and it bears some resemblance with anosodiaphoria (Babinski, 1914). For example, one of our patient was a physician and could very precisely describe the onset of his neurological weakness (a total hemiplegia) and knew that it was caused by a stroke; however, he did not feel the need to call for help or go to hospital for treatment, and he made implausible plans to play golf with his son on weekends. Of course, this schematic typology of four different categories of awareness is not always as strict and clear in clinical practice, possibly because both monitoring systems can be affected at different degrees in different patients. Nevertheless, we believe that this may help to better characterize the behavioral manifestations of AHP, and it should encourage further empirical investigations of the neuropsychological correlates of anosognosia (see Cocchini & Della Sala, Chapter 7; Orfei et al., Chapter 19, this volume).
Interpretations, Beliefs, and Belief Changes Both the implicit ‘‘feeling’’ and explicit ‘‘knowing’’ about motor performance should normally be integrated in a single coherent appreciation, based on the convergence of the different feedback and feedfoward signals, which can be consciously manifested and verbally expressed by the patient. We hypothesize that this function might take place in the left hemisphere and reflect the ‘‘interpreter’’ processes that have been observed in split brain patients (Gazzaniga, 2000). Rational or delusional elaborations under the control of the left hemisphere interpreter could induce the formation of false beliefs that may combine with old or ‘‘default’’ beliefs about one’s health, or with stereotypical biases in self-evaluation. For instance, it is a normal tendency of healthy individuals to overestimate their well-being and underestimate their risk for diseases (Weinstein, 1984, 1987, 1989). A role for this integrative interpreter might
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underlie the frequent rationalization or even confabulations expressed by some patients when they explain away their failures (Assal, 1983; Ramachandran, 1995). However, the existence of biased interpretations or false beliefs may not be sufficient to account for all aspects of anosognosia, since repeated confrontations with the deficit (or at least its consequences) should eventually elicit some signals of uncertainty that could then prompt for an appropriate verification and revision of current beliefs based on new experience. These uncertainty signals might result from cognitive or affective processes activated by monitoring systems, or from higher-level executive systems that are recruited when information provided by the monitoring systems is incongruent or insufficient (Norman & Shallice, 1986). Indeed, a striking feature of anosognosic patients is that such a tendency to check and modify current beliefs seems often to be missing. Despite recurrent confrontations and encounters with caregivers or doctors, they may stick to their interpretation rather than call it into question, despite the obvious self-relevance and emotional significance of a potential deficit. In some sense, these patients behave exactly opposite to those patients with somatoform disorders (e.g. hypochondria) who have exaggerated fears about a possible illness; rather, they appear remarkably easy and unworried about incongruent or missing information concerning their current bodily state. This suggests that cognitive or affective processes necessary for updating old beliefs might also be altered by the lesion. In a recent study (Vocat et al., in preparation), we specifically tested for the ability of patients to change beliefs by asking them to guess a word according to a series of five successive clues, which provided a progressive informative content about the target word. After each clue (even for the first very general one), patients had to propose a word and give their level of confidence from 0 (not sure at all) to 8 (completely sure). We found that anosognosic patients were much more confident for responses to the initial clues than nosognosic patients. Moreover, they tended to perseverate with a first wrong answer even when faced with the incongruency of subsequent clues, typically providing some ‘‘plausible’’ but largely irrelevant connections between their chosen word and the given clues. Nevertheless, after the fifth and last clue, which provided the most specific information about the target word, anosognosic and nosognosic patients were equally successful at finally resolving the riddles, indicating that anosognosics did not have general reasoning deficits but rather that they tended to remain stuck to their false beliefs and failed to modify them, unless clearly incongruent information was given. These findings therefore clearly demonstrate for the first time that anosognosia correlates with a specific disturbance to modify current beliefs, even when these do not rely on sensorimotor feedback and do not concern their motor performance or health. Based on our neuropsychological and anatomical lesion overlap (Vocat et al., in preparation), we speculate that deficits in changing beliefs in anosognosia
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might be associated with lesions in the hippocampus and amygdala, possibly together with connections to medial prefrontal areas involved in self-monitoring (Norman & Shallice, 1986). Damage to these structures might disrupt the encoding of important new information in memory and reduce the normal affective drive to adjust behavior in the face of self-relevant, potentially threatening situations. Damage to the insula and ventromedial prefrontal regions might also play a role in belief formation and belief changes by suppressing affective signals necessary to trigger belief changes (Naqvi & Bechara, 2009). Interestingly, in a recent imaging study that examined decisions based on various beliefs in healthy subjects, activation of the ventromedial prefrontal cortex was associated with accepted beliefs, whereas activation in insula correlated with disbelief and activation in ACC correlated with uncertainty (Harris, Sheth, & Cohen, 2008). In any case, the exact neural substrates of belief systems and impairment thereof will need further investigations.
Psychological Reaction While there is no doubt that anosognosia is the direct result of a multifactorial organic brain dysfunction, it is important to keep in mind that this does not entirely exclude a role for purely psychological dimensions that can influence how individuals will cope with a sudden severe deficit. Defense mechanisms are well known to operate in healthy people, and there is no reason to think that they should always cease to work in stroke patients. The sudden loss of motor and sensory capacities for one’s hemibody and its consequences obviously constitute a major traumatic event, likely to require some psychological coping and defense mechanisms. A phase of acceptance of the deficit and its implications is needed (see O’Callaghan, Powell, & Oyebode, 2006). In addition, another intriguing possibility is that some lesions might affect the recruitment or the efficacy of these defense mechanisms, in either a positive or negative way (Schilder, 1935; Turnbull & Solms, 2007). For example, it is possible that some frontal lesions might abolish an inhibition that normally refrains the use of ‘‘denial,’’ or conversely the lesions might suppress a motivational incentive to refute the acceptance of a deficit. How these psychological factors interact with neuropsychological impairments and modulate the clinical manifestations of AHP is still largely ignored, but they should not be minimized, even though it is certainly obvious that they cannot explain all anosognosic manifestations.
Outlook for Future Research on Anosognosia for Hemiplegia To conclude this section on AHP, we would like to underscore that future models of anosognosia should incorporate a role for several distinct components
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that do not only relate to sensorimotor processing and cognitive appreciation of hemiplegia but should also take into account the role of parallel monitoring systems that encode error signals at different levels of awareness, as well as emotional systems that respond to these error signals and serve to adjust behavior or beliefs based on self-relevant information. Existing data converge to suggest that AHP is likely to result from a combination of several deficits affecting different domains (including proprioception, neglect, memory, belief formation, or verification), with corresponding multifocal neural correlates (including fronto-parietal cortex, premotor areas, insula, and anterior subcortical white-matter), but the exact combination responsible for the different aspects and the different types of AHP still remain to be clarified by large, systematic neuropsychological studies testing specific hypotheses.
Conversion and Hysterical Paralysis Hysteria is a condition characterized by the report of subjective neurological symptoms (e.g., motor paralysis) without any damage to the nervous system, and thus it presents with a number of features that seemingly mirror the manifestations of anosognosia. Whereas AHP involves a lack of awareness, misbeliefs, or denial concerning a ‘‘real’’ deficit due to organic brain damage, and does not result from a more general cognitive impairment or confusion, on the contrary, hysterical paralysis implies a conscious experience, illusion, or conviction of a deficit that is not caused by any organic illness, yet not explained by voluntarily simulation or psychotic delusions (Vuilleumier, 2005, 2009). Hysteria is classified among psychiatric disorders, but many modern views on this condition are derived from the early work of neurologists who also studied anosognosia and pioneered neuropsychological accounts of awareness in the nineteenth century—particularly Charcot (1892) and Janet (1894). Babinski and Dagnan-Bouveret (1912) theorized about the role of emotional triggers in producing motor hysteria prior to Babinski’s seminal case report on anosognosia of hemiplegia (Babinski, 1914), and he actually described the classic eponymous plantar reflex as a new clinical sign to distinguish between organic and hysterical paralysis (see Okun & Koehler, 2004). The contemporaneous work by Freud and Breuer (1895) similarly insisted on a transformation of unconscious emotional disturbances into physical complaints, eventually leading to the current diagnostic category of ‘‘conversion’’ (American Psychiatric Association, 1994) that has nowadays replaced the terminology of hysteria in psychiatry textbooks. However, the exact cognitive and emotional processes underlying such conversion of psychological motives into physical symptoms, as well as their neurophysiological substrates, remain poorly known (Kozlowska, 2005; Vuilleumier, 2005, 2009). Unlike other psychiatric conditions, hysterical conversion has been only rarely studied using neurophysiological or
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neurocognitive approaches. In this section, we will review those theoretical accounts that have attempted to attribute conversion disorders to a dysfunction of specific neural circuits and, most particularly, summarize a few recent studies that applied brain imaging techniques to identify the functional neural correlates of hysterical paralysis.
Hysterical Conversion in Neurology Hysterical conversion is still encountered by neurologists and represents 1%–4% of patients admitted to neurological wards (Krem, 2004). Different studies conducted in different periods and different hospitals have revealed a relatively stable rate across decades since the early half of the past century, despite changes in some of the predominant clinical manifestations (Frei, 1984; Mace, 1992; Perkin, 1989; Trimble, 1981). Like anosognosia, conversion most often involves motor or sensory functions, such as hemiplegia, paraplegia, or anesthesia, but also visual loss, amnesia, or even language disturbances and pseudo-dementia (e.g., Ganser syndrome). Moreover, several studies have suggested that motor conversion involves left limbs much more frequently than right limbs (Galin, Diamond, & Braff, 1977; Stern, 1983), just like AHP, suggesting that conversion symptoms might reflect an interaction in hemispheric asymmetries for motor control, emotional processing, and consciousness (FlorHenry, 1978; Miller, 1984). However, other recent studies did not replicate this asymmetry (Stone et al., 2002; Stone, Warlow, Carson, & Sharpe, 2003) and motor symptoms may be observed on either side (Vuilleumier, 2005; Vuilleumier et al., 2001). Further, as emphasized by Freud, neurological symptoms in conversion hysteria may not respect the topographical organization of the nervous systems but more subjective or symbolic representations, and thus produce distinct atypical clinical manifestations such as glove anesthesia or tubular vision. Although several neurological signs might be used to distinguish between organic and nonorganic deficits, including Babinski sign (Okun & Koehler, 2004) or Hoover sign (Koehler & Okun, 2004), there is no straightforward criteria or reliable ‘‘objective’’ sign to establish the diagnosis of conversion symptoms (Krem, 2004). In particular, the notion that conversion patients often present with a good acceptance of their symptoms (so called ‘‘belle indifference’’) has been shown to be relatively nonspecific (Vuilleumier, 2009). In fact, many of these patients may present with some emotional distress rather than emotional indifference; furthermore, a lack of concern is also frequent in anosognosic patients who do have a severe deficit. In addition, although hysterical symptoms are generally thought to result from a response to stressful situations or emotional eliciting factors (Binzer, Andersen, & Kullgren, 1997; Roelofs, Spinhoven, Sandijck, Moene, & Hoogduin, 2005), assessing their importance and relation to the symptoms may be highly dependent on subjective
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judgments by the clinician, and their causal role (or even existence) is therefore sometimes difficult to ascertain. Conversely, many patients with organic neurological diseases may also report stressful conditions preceding a ‘‘real’’ neurological illness, as shown for instance for stroke (House, Dennis, Mogridge, Hawton, & Warlow, 1990) or multiple sclerosis (Mohr, Hart, Julian, Cox, & Pelletier, 2004). Thus, the diagnosis of conversion is typically made after an exclusion of various potential organic diseases, requiring negative findings from a large range of clinical exams, including magnetic resonance imaging (MRI), electroencephalogram (EEG), electromyogram (EMG), transcranial magnetic stimulation (TMS), cerebrospinal fluid (CSF) tap, blood tests, and so forth. A better understanding of the cognitive and neurobiological mechanisms of conversion might therefore be useful to improve the assessment of these patients, because the accrual of many negative tests may not only cause discomfort but also worsen psychological distress and fears in these patients; and diagnosis by exclusion may prove difficult in some situations with mixed pathologies (Krem, 2004; Vuilleumier, 2009). This is all the more problematic since a mixture of conversion hysteria with a ‘‘true’’ organic neurological disease may sometimes occur. For example, the presence of ‘‘typical’’ psychogenic conversion symptoms has been reported in patients with acute stroke (Gould, Miller, Goldberg, & Benson, 1986), multiple sclerosis (Nicolson & Feinstein, 1994), or after closed head injuries (Eames, 1992). These symptoms included exaggerated or non-neurological complaints, changing deficit, patchy or inconsistent distribution, as well as lack of concern. Interestingly, a large study in 167 patients found that such symptoms were most often seen in patients who had diffuse brain lesions (e.g., closed head injury, anoxia, encephalitis) or subcortical focal strokes, and correlated with the presence of extrapyramidal motor disorders (Eames, 1992), suggesting that a disconnection of cortico-subcortical pathways might contribute to produce dissociative experiences in the conscious motor control of these patients. A coexistence of hysterical conversion and organic neurological disease is also frequently seen in patients with epilepsy who may occasionally present with pseudo-seizures (Devinsky, 1998), possibly reflecting an influence of their past neurological illness on their response to emotional distress (Brown, 2004; Miller, 1987). Such mixture of organic and psychogenic symptoms obviously complicates the clinical diagnosis of conversion made on exclusion criteria only. Importantly, although early studies reported that some patients with hysteria symptoms may develop a real neurological disease after several years (Mace & Trimble, 1996), a number of careful follow-up studies have clearly shown that such evolution is very uncommon (Crimlisk et al., 1998; Stone, Sharpe, Rothwell, & Warlow, 2003). Very few patients ( During unilateral deficit
Thalamus
Caudate 88
Adjusted rCBF values
75 74
Putamen
Z = 3.81
60
Z = 3.78
73 71
Z = 5.14
86
58
72
87
85
56
84
70 54
69 68
83
52
82
50
81
67 66 65
80
Deficit Recovery (T1) (T2)
Deficit Recovery (T1) (T2)
Deficit Recovery (T1) (T2)
Figure 17.4 Brain regions showing decreased activity in the hemisphere contralateral to unilateral sensori-motor loss due to conversion hysteria (n ¼ 7 patients). Comparing activation after recovery and during symptoms revealed significant changes in caudate nucleus, putamen, and thalamus, corresponding to major relays within the basal gangliathalamo-cortical loops that control movement initiation. (Adapted from Vuilleumier et al., 2001, with permission from Oxford University Press, Brain, 124, 1077–1090.) (See Color Plate 17.4)
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to various functions, including not only behavioral inhibition (Lhermitte, Pillon, & Serdaru, 1986) but also emotional control (Bush, Luu, & Posner, 2000), selfreferential memory (D’Argembeau et al., 2005), and belief judgments (Harris, Sheth, & Cohen, 2008). The exact role of cingulate and ventromedial prefrontal activity in hysterical conversion therefore remains to be further clarified. In a recent single case study, we specifically tested for a contribution of active motor inhibition processes during hysterical paralysis (Cojan, Waber, Caruzzo, & Vuilleumier, 2009), by designing a new go-nogo task that allowed us to compare different motor processes for both the normal and affected limb, including motor preparation, execution, and inhibition. The patient was a young woman with a left hand weakness following a minor illness occurring in a period with several stressful life events. She underwent fMRI during a simple motor task, in which each trial began with the presentation of a picture of a hand (left or right), instructing the patient to prepare a movement on the corresponding side, which was then followed by either a go signal (requiring execution of the prepared movement) or a nogo signal (requiring inhibition of the prepared movement). This design allowed us to determine any similarities between a failure to move the affected hand (on a left go trial) and a normal voluntary inhibition of movement (on left or right nogo trials). A large body of literature in neuroimaging and neuropsychology has linked motor inhibition to the right inferior frontal gyrus (rIFG), for both motor and nonmotor cognitive tasks (Aron, 2007; Xue, Aron, & Poldrack, 2008), such that rIFG was predicted to be specifically activated by motor inhibition at least during nogo trials. In our patient, preparation induced a normal and symmetric pattern of activation of the contralateral motor cortex (Figure 17.5B), just like healthy controls (Figure 17.5A). This finding confirms intact motor imagery and intact motor intentions despite hysteria. During execution, the patient showed normal motor activation for the intact hand, but no activation in motor cortex for the affected limb (and no actual movement). Critically, she did not activate the rIFG on the left-go trials, even though she did not make any movement, whereas the rIFG was normally activated by inhibition on nogo trials in her case (with the right hand) as well as in healthy controls (for both their right and left hands). Importantly, this result reveals that the left hand paralysis did not recruit voluntary inhibitory processes mediated by rIFG. However, unlike healthy controls, the patient also selectively activated anterior and posterior midline brain regions, including the ventromedial prefrontal cortex (vmPFC) during execution attempts with the affected hand (left go trials), and both the ventromedial PFC and precuneus during preparation of left hand movements. In addition, connectivity analysis again revealed that the vmPFC was specifically coupled with the right motor cortex (contralateral to the paralyzed hand) but not with the left motor cortex (contralateral to the intact hand). Finally, we investigated a group of healthy volunteers who were asked to feign a left hand paralysis during the same task (Cojan, Waber,
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Caruzzo, & Vuilleumier, 2009). However, the simulation of paralysis on leftgo trials was found to produce exactly the same pattern of brain activity as the voluntary withholding a response on nogo trials (see Figure 17.5C), clearly demonstrating that hysterical paralysis was distinct from simulation.
Figure 17.5 Brain regions activated during a go-nogo motor task performed with either hand. In a group of 12 healthy subjects (A) and a patient with left hysterical paralysis (B), preparing a movement activated the contralateral motor cortex symmetrically for both the right and left hand. Motor cortex was also activated by execution (go trials) with either hand in healthy subjects, and with the intact right hand in the patient; however, a failure to move the hand on left go trails in the patient produced no increase in motor cortex but selective activation in precuneus and prefrontal areas. Importantly, the right inferior frontal gyrus (IFG) was activated by motor inhibition on nogo trials in healthy subjects but not during failures of movement on left go trials in the patient. The precuneus and ventromedial prefrontal cortex (PFC) were selectively activated by left-hand trials compared to right-hand trials. (C) Activation is plotted for the right IFG (shown in A) in normal controls, subjects simulating a left-hand paralysis, and the patient with left motor conversion (three panels from left to right, respectively); and for the ventromedial PFC (shown in B) in the patient. (Adapted from Cojan et al., 2009, with permission from Elsevier, NeuroImage, 47(3), 1026–1037.) (See Color Plate 17.5)
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We also compared this pattern of activation in conversion with another situation where left arm paralysis was induced by hypnosis in a group of healthy volunteers who then had to perform the same go-nogo task in different states (Cojan et al., 2009). Changes in brain activity were clearly different between conversion and hypnosis for vmPFC (increased for all left hand actions in conversion) and for rIFG (increased for all conditions in hypnosis), while there was a similar increase of precuneus activity for all left hand actions during both hypnosis and conversion. These data suggest that hypnosis may also involve mental imagery and self-related memory processes that are subserved by the precuneus (Cavanna & Trimble, 2006; Lou et al., 2004), but they imply a distinct modulation of executive monitoring systems in right IFG. Interestingly, activity in the precuneus has also been related to unconscious intentional biases in choices and actions (den Ouden, Frith, Frith, & Blakemore, 2005; Soon, Brass, Heinze, & Haynes, 2008). Another study also reported an activation of anterior cingulate cortex during hypnotic suggestion of paralysis (Halligan, Athwal, Oakley, & Frackowiak, 2000), but this was interpreted as the source of inhibition on motor actions. Taken together, these imaging studies therefore converge to demonstrate that conversion symptoms may lead to functional changes in brain areas concerned with the affected sensorimotor domain, and they clearly differ from mere simulation. Conversion paralysis may involve a suppression of motor processes in basal ganglia-thalamic loops through the influence of medial parietal or ventromedial prefrontal areas, which could in turn impact on primary motor cortex depending on the exact task requirements. Because motor cortex can still be activated by intentions and imagery, a suppression of activity in downstream basal ganglia loops might correspond to the subjective feeling of patients that their volition is preserved, but their execution is ‘‘blocked.’’ In addition, conversion paralysis does not seem to result from an active inhibition by the right inferior prefrontal cortex as seen in classic nogo tasks, but rather it involves an increased activity and increased coupling with precuneus and ventromedial PFC. As the latter regions are thought to be particularly involved in self-related representations, imagery, belief checks, and emotion regulation, these results suggest that the primary motor cortex and afferent pathways might be abnormally influenced by internal processes related to self-processing rather than by the normal premotor mechanisms in dorsolateral and dorsomedial prefrontal regions.
Conclusions Anosognosia and conversion hysteria have raised a number of fascinating questions on the mind–brain relationship for more than a century, and both still are puzzling clinical conditions in neurology. Various hypotheses have been put
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forward to account for the striking dissociation between self-awareness and body states observed in these two disorders, but often on the basis of theoretical speculations rather than empirical investigations. With the advent of new neuroimaging techniques for advanced anatomical lesion analyses and functional brain mapping, we are now just beginning to unravel the interaction of multiple cognitive and affective processes that are likely to jointly contribute to produce such distortion in awareness. In this review, we have argued that distinct patterns of AHP might result from losses in sensorimotor feedback combined with lesions affecting neural pathways responsible for different types of monitoring of motor errors, possibly operating at either explicit or implicit levels, together with additional lesions in cognitive and affective systems responsible for appropriate behavioral adjustment and learning (hence contributing to deficits in complex mental processes underlying belief formation, verification, or self-concern). This constellation corresponds to the presence of multifocal neural correlates (e.g., in parietal cortex, premotor areas, insula, etc.) typically caused by large lesions or dysfunction after stroke. We have also suggested that this obdurate unawareness for motor deficits in AHP might be mirrored by the seemingly imaginary experience of motor impairment in conversion hysteria. We showed that the latter might involve functional changes in cortico-subcortical motor pathways, combined with an activation of limbic regions and midline frontoparietal areas (including ventral prefrontal regions, ACC, precuneus, and perhaps amygdalo-hippocampal structures), which have previously been associated with self-related representations in imagery, memory and belief state presentation, and memory, and could impose inhibitory or modulatory influences on the motor pathways due to some emotional states in patients with conversion hysteria. However, it remains to be determined whether the mirror symptoms in anosognosia and conversion hysteria might correspond at least partly to mirror changes in some brain regions, and which neural networks and cognitive mechanisms might be concerned by both conditions, if any. Based on our framework proposed to account in AHP, it would be tempting to extend the putative mechanisms responsible for losses of awareness to mirror disturbances resulting in productive symptoms rather than losses (see Figure 17.6). Thus, implicit monitoring processes conveying unconscious signals of motor errors might not only fail to activate in the presence of a deficit (as in AHP) but also produce abnormal signals in the absence of a corresponding deficit, leading to kinesthetic illusions (Feinberg et al., 2000; Lackner & DiZio, 1992; Naito et al., 2007) and limb reduplication syndromes (Halligan, Marshall, & Wade, 1993; Vuilleumier, Reverdin, & Landis, 1997) when explicit monitoring remains intact; or leading to frank somatoparaphrenia when explicit awareness of the deficit is lacking (Critchley, 1964; Halligan, Marshall, & Wade, 1995; Vallar & Ronchi, 2009). Conversely, a false perception of motor deficit might be delivered to conscious awareness by explicit
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Explicit/Conscious pathway Attention, proprioception, vision, etc Fronto-parietal cortex Good
Abnormal
No signal
Full Anosognosia
Anoso diaphoria
Alien control (schizophrenia)
Good
Partial Anosognosia
Full Awareness
Hypnosis
Somatoparaphrenia
Kinesthetic Illusions
Hysteria
Abnormal
Implicit / Unconscious pathway Affect, motivation, error signals Insula, ACC, VMPFC
No signal
Figure 17.6 A schematic classification of impaired body awareness in different conditions. A putative role is shown for explicit/conscious and implicit/unconscious monitoring processes in relation to each condition, as an attempt to extend our account of motor monitoring deficits in anosognosia for hemiplegia to hysteria and other disorders. Both conscious and unconscious systems can possibly show different degrees of activity resulting in either abolished, normal, or abnormal signals about body states. ACC, anterior cingulate cortex; VMPFC, ventromedial prefrontal cortex.
monitoring processes during conversion hysteria or hypnosis, perhaps with a concomitant abnormal error signal in implicit pathways in hysteria (Sackeim, Nordlie, & Gur, 1979; Vuilleumier, 2005) but not hypnosis (corresponding to the typical dissociative state observed in the latter case); whereas abnormal motor signals in awareness with a loss of implicit motor error signal might possibly correspond to the delusion of alien motor control in schizophrenia and other psychosis (Spence, 2002). However, such a classification remains speculative and will need further systematic investigations to be verified and refined. In summary, neuropsychology and neuropsychiatry encompass a vast number of disorders that imply a distortion in self-awareness and self-monitoring, ranging from insufficient or absent appraisal of current bodily states to exaggerated or even illusory experiences. We believe that a better understanding of mechanisms underlying such disorders is necessary not only to gain insight into some of the most fascinating facets of human consciousness but also to improve the clinical assessment, management, and rehabilitation strategies for these patients.
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Acknowledgments This work was supported by grants from the Swiss National Foundation (32003B-108367 and 32003B-114014) and Geneva Academic Society to PV, as well as a fellowship from the Foundation Boninchi to RV. We thank Fabienne Staub, Julien Bogousslavksy, and Theodor Landis for their support during our work.
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Measurement Issues and Technology
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Functional Imaging of Self-Appraisal Sterling C. Johnson and Michele L. Ries
Ideas or schemas that one possesses about his or her own capabilities, aptitudes, and traits constitute an aspect of personal semantic knowledge that is integral for selecting adaptive and appropriate goal-directed behavior (Showers & ZeiglerHill, 2003). The study of such first-person schemas and their development has been a long-standing area of psychological inquiry (James, 1890; Kagan, 1982; Leary & Price Tangney, 2003; Nelson & Fivush, 2004). Other chapters of this book are primarily concerned about self-schemas that were once, but are no longer accurate due to brain injury or disease. In contrast, the primary focus of this chapter is the use of functional imaging methods to examine the normative capacity for reflective thought and appraisal of self-schemas. This capacity is metacognitive in the sense that William James described it—the ‘‘I’’ experiences and evaluates the ‘‘me’’ (James, 1890). In a prior review (Schmitz & Johnson, 2007) we described evidence from a wide range of affective, cognitive, and social neuroimaging research converging on a system of brain regions important broadly for appraising the self, self-relevant features of the environment, the contents of mind, and social interaction (see also Amodio & Frith, 2006). In that previously presented framework, we described the literature regarding overlapping and interacting brain networks in these kinds of self-appraisal. The anterior cingulate, ventromedial prefrontal cortex, insula, basal forebrain, and other subcortical regions were presented as a network responsible for bottom-up detection of salient, self-relevant intero- and exteroceptive stimuli. We had also proposed that dorsal aspects of anterior cingulate, medial prefrontal cortex (MPFC) extending along a ventral-dorsal axis, and the posterior cingulate instantiate top-down metacognitive evaluation of one’s own behaviors, the behavior of others, and the interpretation of dynamic feedback during social interaction (see Figure 18.1, which is adapted from Schmitz & Johnson, 2007). In the present chapter we describe in more detail this latter metacognitive proposal and summarize experiments from our functional imaging laboratory and the wider literature that identify brain regions involved in self-appraisal. 407
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Figure 18.1 Loci of activations resulting from multiple neuroimaging task domains that require introspective appraisal of stimuli with self-relevant features. Squares indicate appraisal of one’s own personality traits, personal morals, opinions, attitudes, visuospatial perspective, personal preferences (Craik et al., 1999; Cunningham, Raye, & Johnson, 2004; Greene, Nystrom, Engell, Darley, & Cohen, 2004; Greene, Sommerville, Nystrom, Darley, & Cohen, 2001; Jacobsen, Schubotz, Hofel, & Cramon, 2006; Johnson et al., 2002; Johnson et al., 2005; Kelley et al., 2002; Moll et al., 2002; Schmitz & Johnson, 2006; Schmitz et al., 2004; Seger, Stone, & Keenan, 2004; Vogeley et al., 2004; Zysset, Huber, Ferstl, & von Cramon, 2002; Zysset, Huber, Samson, Ferstl, & von Cramon, 2003). Circles indicate appraisal of reaction to affective stimulus content (Gusnard et al., 2001; Moll et al., 2002; Ochsner et al., 2004). (Adapted with permission from Schmitz & Johnson, 2007, with permission from Elsevier, Neuroscience and Biobehavioral Reviews, 31(4), 585–596.) (See Color Plate 18.1)
In the following sections, we first discuss the way in which results of functional neuroimaging studies provide information complementary to that derived from lesion studies. Together these experimental approaches can yield a more comprehensive understanding of the brain substrate of self-evaluative processes. Second, we present results of functional magnetic resonance imaging (fMRI) studies from our research on self-appraisal. For details of the participants, task parameters, and statistical analysis in all studies presented, the reader is referred to the original papers, which are cited. Third, we present task-dependent and functional connectivity findings that provide insight into putative brain networks supporting selfappraisal. Fourth, we show how we have extended our findings from normative fMRI studies to the investigation of functional brain changes that accompany anosognosia in traumatic brain injury (TBI) and amnestic mild cognitive impairment patients. Since the work presented in this chapter is heavily dependent on functional MRI (fMRI) methodology, the chapter closes with a discussion of task design and interpretive considerations in fMRI research—both in the study of normative self-appraisal and in patients with anosognosia.
Functional Neuroimaging and Lesion Studies Studies of patients with neurologic damage and functional neuroimaging studies of both cognitively healthy and neurologically impaired people provide complementary information for understanding the brain substrates of accurate
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self-appraisal and anosognosia. Most of what we know about brain–behavior relationships has been rooted in lesion work—with functional neuroimaging serving an attendant role in adding to this body of knowledge. However, functional neuroimaging (including blood oxygen level–dependent [BOLD] fMRI) offers the unique ability to assess brain correlates of behavior in the intact brain. Furthermore, examples exist in which functional neuroimaging has arguably been the foremost method responsible for furthering knowledge of localized brain functions. One example of this is the contribution of fMRI to our current knowledge regarding the posterior cingulate cortex’s (PCC) involvement in self-appraisal—as well as this region’s related role in episodic recognition memory. Before the advent of functional neuroimaging, it was difficult to assess PCC function in humans, largely due to the rarity of selective pathological lesions in this brain region (Valenstein et al., 1987; Vogt & Laureys, 2005; Vogt, Vogt, & Laureys, 2006). Functional neuroimaging in cognitively healthy adults over the past decade has rapidly propelled our understanding of the PCC’s role in self-appraisal—showing reliable evidence that this region, together with the MPFC, is active during fMRI tasks in which people appraise their own traits, opinions, attitudes, and preferences (see Figure 18.1). Imaging tools such as fMRI promise not only to inform us about the functional specialization of brain regions, but they are also uniquely suited to provide information about how regions across the brain may operate in synchrony (i.e., condition-dependent connectivity and functional connectivity) in service of behavioral functions such as self-appraisal. This approach to understanding behavioral phenomena such as self-appraisal and anosognosia in terms of networks of brain activity is critical since brain regions do not operate in isolation—the activity (and/or degeneration) of one brain region affects the function of other interconnected brain regions. In subsequent sections of this chapter, we will describe how functional connectivity is measured, and the implications it may have for understanding self-appraisal and anosognosia.
Functional Magnetic Resonance Imaging Studies of Self-Appraisal in the Intact Brain Brain Activity during Self-Evaluation When a patient is asked to describe his or her symptoms, he or she is essentially being asked to make a self-evaluative decision that is metacognitive. Similarly, self-report surveys of mood or physical symptoms require an evaluation or appraisal of some aspect of oneself on specific symptom dimensions. An initial study from our lab investigated fMRI activity associated with self-reflection (Johnson et al., 2002) in 11 right-handed cognitively healthy adults (mean age: 35 years). The experimental condition of the fMRI task required participants to rate themselves on simple statements regarding traits, attributes, and abilities
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Figure 18.2 Midsagittal view of each participant showing prefrontal activation during self-reflective thought. The activations are superimposed on top of each participant’s anatomical scan. Note the consistent activation of the prefrontal cortex across subjects. For the purposes of this display, the statistical threshold was set to an uncorrected p-value of .0005. These results are prior to any spatial standardization. (Adapted from Johnson et al., 2002, with permission from Oxford University Press, Brain, 125(Pt 8), 1808–1814.) (See Color Plate 18.2)
that required a yes/no decision and were in the style of questions found on the Minnesota Multiphasic Personality Inventory. The control condition involved retrieval of general factual knowledge. Functional magnetic resonance imaging was performed at Barrow Neurological Institute on a 1.5 Tesla scanner. The results revealed a pattern of brain activation that was strikingly robust in single participants and highly consistent across participants (i.e., the kind of consistency one might see with a language or sensory motor paradigm was also observed in this self-appraisal paradigm). Figure 18.2 depicts a midsagittal slice from each of the 11 subjects. Strong BOLD signal was consistently observed in the anterior medial frontal lobe and posterior cingulate. Despite the robust fMRI signal, the behavioral phenomenon associated with this signal required further definition: it was unclear at this point whether fMRI activity associated with this task was primarily associated with self-reflection or represented more general metacognitive processes. Further, it was unclear whether the subjective/ambiguous nature of the self-appraisal condition was driving the result. We therefore constructed other fMRI tasks to address these issues.
Self-Evaluation versus Other Evaluation: Similarities and Distinctions in Regional Brain Activity In a second study (Schmitz, Kawahara-Baccus, & Johnson, 2004), our goal was to determine similarities and distinctions in brain response during evaluation of
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oneself versus evaluation of a significant other (e.g., a close friend or relative). The paradigm employed in this study required the 19 young adult, cognitively healthy participants to make yes/no responses to trait adjectives to questions in three conditions: (1) self-evaluative (does the word describe me?), (2) other-evaluative (does the word describe my close friend?), (3) semantic (is the word positive?). First, we found a highly similar pattern of results involving the MPFC and PCC when compared to the Johnson et al. (2002) study (see also Craik et al., 1999). This finding held regardless of whether the subject was appraising characteristics of oneself or a significant other. Ostensibly this suggests a more general metacognitive role for these structures that was not necessarily specific to the self. However, simulation theory would suggest that making inferences about a close other person still invokes self-referential processes (for an excellent description of this idea, see Mitchell, Banaji, & Macrae, 2005). Using a similar paradigm to the one we used, D’Argembeau et al. (2008) asked healthy subjects to appraise the self and significant other for a current time period and for a time period in the past. Similar to our result and supportive of Mitchell’s hypothesis, they found cortical midline activations for all four conditions, though a greater degree of activation was found during the current self-appraisal condition. The second major finding from Schmitz et al. (2004) was that when the ‘‘self’’ versus ‘‘other’’ conditions were directly compared, greater activity was observed in the right prefrontal cortex (see Figure 18.3, see also Kaplan, Aziz-Zadeh, Uddin, & Iacoboni, 2008) consistent with anosognosia lesion studies reviewed elsewhere
Figure 18.3 Random-effects group analysis indicating greater blood oxygen level– dependent (BOLD) signal during self-evaluation versus other evaluation. The main effect of activation occurred in the right dorsolateral prefrontal cortex (maxima t ¼ 7.44, corrected false discover rate ¼ 0.013; x, y, z ¼ 26, 52, 16; cluster ¼ 202). (Adapted from Schmitz et al., 2004, with permission from Elsevier, NeuroImage, 22(2), 941–947.) (See Color Plate 18.3)
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in this book. This is supportive of the idea that the right more than the left frontal cortex contributes to self-representation.
Are Medial Prefrontal Cortex and Posterior Cingulate Cortex Activations Explained by Subjective Decisions That Are Not Necessarily Related to Self-Evaluation? In Johnson et al. (2005) we examined the question of whether subjective decision making alone can account for the results in the anterior MPFC and PCC reported above. An important psychological factor that had been common to many prior experiments activating the MPFC is subjective evaluation—that is, making a decision when there may not be an externally verifiable correct answer. This subjectivity factor, regardless of self-relevance or emotional connotation, needed to be ruled out as the explanatory source of midline activation in our prior studies. To address this, we performed a study in 16 healthy young adults. The task required participants to decide which of two colored squares best matched a target square under different conditions. In condition 1, the decision was external and based on the color similarity between the target and the choice alternatives. This was an objective decision and was rather easy. In condition 2, the decision, though still external regarding color similarity, was difficult and subjective. In fact, the two choice alternatives were equally distant in color hue and intensity from the target color square. The equivalence among the choice alternatives meant that the answer was ambiguous, and the decision would be entirely subjective. A third condition was presented in which the participant was asked to rate which of the two choice colors was preferred with the target color. This was also a subjective choice, but now the reference was internal (a personal self-preference), rather than external (color similarity). The participants were cognitively healthy young adults (mean age: 23 years) who were able to understand the instructions and completed the task without difficulty. The results indicated the following: the similarity decision (external: ambiguous versus easy) resulted in activations in the midcingulate and lateral parietal lobes (intraparietal sulcus), and inferior frontal and lateral orbital frontal lobes (the midcingulate activation is highlighted in the top panel of Figure 18.4). The MPFC and posterior cingulate cortices were not active in that contrast. The preference decision versus the ambiguous similarity decision (both conditions required subjective decisions, but differed with regard to the referent) revealed differential activation in the left MPFC and posterior cingulate and bilateral head of caudate nucleus (the posterior cingulate activation is highlighted in the bottom panel of Figure 18.4). These results—derived from an fMRI task that controlled for subjective decision making in the comparison condition—indicate that anterior MPFC and PCC responsivity was driven by an evaluation that requires processing about oneself and not simply subjective decision making.
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Figure 18.4 Statistical Parametric Map in 16 subjects during subjective decisions. (Top) Ambiguous/subjective vs. nonsubjective color similarity decision making. (Bottom) Preferential subjective versus ambiguous/subjective decisions. (Adapted from Johnson et al., 2005, with permission from MIT Press, Journal of Cognitive Neuroscience, 17(12), 1897–1906.) (See Color Plate 18.4)
Functional Magnetic Resonance Imaging ConditionDependent and Functional Connectivity: Two Methods Informing Normative Brain Activity Important for Self-Appraisal Condition-Dependent Connectivity during Self-Appraisal Results from our lab and others show that the MPFC is consistently active during personally salient decision making (e.g., Figure 18.1, see also Northoff et al., 2006)—MFPC activity elicited in fMRI tasks targeting this psychological construct using diverse stimuli (from pain to reward to physical attractiveness) (Northoff et al., 2006; Schmitz & Johnson, 2007). However, networks of brain regions that exhibit condition-dependent relationships during self-reflective tasks (i.e., condition-dependent connectivity) are less defined. In one fMRI self-appraisal study (Schmitz & Johnson, 2006), we examined condition- and region- dependent correlations with more-distant brain regions. Using a self-appraisal decision-making task with two conditions (self-evaluative versus semantic decision), we presented trait adjectives and asked participants to decide whether the word described them (selfevaluative condition), or whether the word had a semantic positive connotation
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Figure 18.5 A group analysis (n ¼ 15) of activation on the Self Appraisal task. Functional connectivity analysis allows one to use a seed region (i.e., the MPFC) and determine regions elsewhere in the brain where signal changes are highly correlated with the seed on the SA task condition but not the other. The ventral MPFC demonstrated coupling with nucleus accumbens, left amygdala, and insula, whereas the dorsal MPFC was selectively coupled with the right dorsolateral prefrontal cortex (dLPFC) and anterior hippocampus bilaterally. Amg, amygdala; aMPFC, anterior medial prefrontal cortex; HF, hippocampus; Nacc, nucleus acumbens. (Adapted from Schmitz & Johnson, 2006, with permission from Elsevier, NeuroImage, 30, 1050–1058.) (See Color Plate 18.5)
(semantic condition). The results revealed task-dependent relationships between the ventral anterior MPFC and the amygdala, insula, and nucleus accumbens; we also showed dorsal anterior MPFC condition-dependent connectivity with dorsolateral prefrontal cortex (PFC) and bilateral hippocampi (see Figure 18.5). In the context of our self-appraisal task, the term ‘‘condition-dependent connectivity’’ means that these regions showed correlated activity during the self-appraisal condition, but not the comparison (semantic decision) condition. This type of effect reflects an interaction in the way that brain regions correlate with each other as a function of task. The MPFC networks identified in this study may subserve distinct contributory processes inherent to self-appraisal decisions, specifically a dorsally mediated cognitive and a ventrally mediated affective/self-relevance network. This proposition regarding regional functional specialization within the MPFC is consistent not only with the results of other neuroimaging studies but also with a large literature on the behavioral effects of lesions localized to ventral versus dorsal medial frontal lobe (Schmitz & Johnson, 2007).
Functional Connectivity: Overlap in Brain Regions Showing Activity during Self-Appraisal and ‘‘Default Mode’’ Connectivity In healthy adults, several networks of functionally related brain regions show spontaneous and coherent low-frequency fluctuations in BOLD signal (i.e.,
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Figure 18.6 Neuroanatomic overlap of functional magnetic resonance imaging activity during a self-appraisal and functional connectivity during ‘‘resting’’ scans (A and B: pFWE > .001): (A) functional connectivity map using posterior cingulate cortex seed region, (B) main effect of self-appraisal task, (C) map from (A) overlaid on map from (B). Blue: regions showing only self-appraisal main effect; red: regions showing only functional connectivity with posterior cingulate cortex; purple: areas of overlap. (From Johnson & Ries, unpublished data.) (See Color Plate 18.6)
functional connectivity). One such functional network, often termed the ‘‘default mode network’’ (DMN), comprises dorsomedial and ventromedial prefrontal cortex, anterior and posterior cingulate cortices, retrosplenial cortex, precuneus, lateral parietal cortices, and mesial temporal lobes (Greicius, Krasnow, Reiss, & Menon, 2003; Raichle et al., 2001; Raichle & Snyder, 2007). Based on the overlap of cortical midline regions showing fMRI activity during self-referential processing and regions showing DMN connectivity (see Figure 18.6), several behavioral neuroscientists have posited that functional connectivity within DMN regions reflects evaluative processing regarding oneself and monitoring one’s relation to the outside world (Gusnard, Akbudak, Shulman, & Raichle, 2001; Gusnard & Raichle, 2001; Raichle et al., 2001). Results of a recent, well-behaviorally-controlled investigation of fMRI ‘‘rest’’ conditions suggest that both MPFC and PCC activity during low-cognitive-demand conditions relates to intentionally balancing attention between the external environment and the appraisal and regulation of one’s behavior in the MRI scanner environment itself (Gilbert, Simons, Frith, & Burgess, 2006). Those results suggest that people ‘‘resting’’ in the scanner are engaged in self-referential processes (such as the self-regulation required to keep still in a confining loud space—the bore of the MRI) during so called ‘‘low-level’’ states.
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To add to published data assessing the claim that DMN functional connectivity relates to self-evaluative processing, we collected ‘‘resting" fMRI data (i.e., scan data acquired while participants lay still in the scanner with eyes closed) in 22 cognitively healthy adults. This yielded data for DMN functional connectivity analysis. We also collected data from a block-design fMRI selfappraisal task in 91 cognitively healthy adults. A primary goal of our study was to more directly examine the neuroanatomic overlap between the statistical parametric map of DMN functional connectivity and the statistical map of fMRI response to the self-appraisal task. We used a seed-region-based approach for our functional connectivity analysis of ‘‘resting’’ data. In this type of analysis, BOLD signal is extracted from a region of interest. Using this extracted data, a Pearson’s product-moment correlation coefficient is calculated between the regional mean of seed region time courses and the time course for each voxel in the whole brain. We defined two seed regions in cortical midline regions shown to be active during self-appraisal: the posterior cingulate cortex and MPFC. The self-appraisal fMRI task consisted of two conditions and was identical to the one described above (Schmitz & Johnson, 2006). In the self-appraisal (SA) condition, participants viewed trait adjectives and made yes/no button press responses to the question: ‘‘Does the word describe me?’’ In the semantic decision (SEM) comparison condition, participants viewed trait adjectives and made button press responses to the question: ‘‘Is the word positive?’’ The statistical contrast of interest in our random effects analysis (a one-group t test) examined the group effect of self-appraisal (SA > SEM). Our main results—depicted in Figure 18.6—indicate that there is striking neuroanatomic overlap between regions active during self-appraisal and regions of DMN functional connectivity. Figure 18.6A shows DMN functional connectivity using the PCC seed; Figure 18.6B shows fMRI activity associated with self-appraisal, and Figure 18.6C shows regions of overlap between these maps (overlap in purple). The data presented here in the context of the existing literature suggest that PCC-MPFC functional connectivity—a central aspect of the DMN—may reflect intrinsic brain activity important for intact self-referential processing. This hypothesis has yet to be fully tested. One way to test this hypothesis is to study the degree to which DMN connectivity is diminished in individuals with anosognosia. We are currently studying this hypothesis.
Extending Results of Normative Self-Appraisal Studies to Anosognosia in Patients Mild Cognitive Impairment As noted by Starkstein and Power (Chapter 10, this volume), anosognosia for impairment of cognitive and functional abilities is present in many patients with Alzheimer’s disease. Recent research suggests that anosognosia for cognitive
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impairment in mild cognitive impairment (MCI) patients may be an important prognostic index, with one report indicating that MCI patients lacking awareness of cognitive and functional deficits show increased incidence of progressing to Alzheimer’s disease over a 2-year period than those who show awareness (Tabert et al., 2002). In a recent fMRI study, we (Ries et al., 2007) investigated MCI participants’ brain activity associated with self-referential processing. As noted earlier in this chapter, the MPFC and PCC—cortical midline structures—are strongly implicated in this metacognitive function. In Ries et al. (2007), it was hypothesized that MCI participants’ activation of cortical midline structures during self-appraisal would covary with their level of insight into their cognitive difficulties. The study examined the correlation between awareness of deficit in amnestic MCI patients and BOLD response during a self-appraisal fMRI task. In this fMRI study, we used a blocked-design fMRI task that reliably evokes cortical midline activity in healthy controls (i.e., the same task used in our analysis of condition-dependent connectivity). Our behavioral evaluation of participants’ level of awareness was based on a discrepancy score between two parallel forms of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). This questionnaire contains items querying changes (ranging from ‘‘much improved’’ to ‘‘much worse’’) over the past 10 years in one’s memory ability (e.g., ‘‘Remembering things that have happened recently’’) and daily problem-solving ability and adaptive functioning (e.g., ‘‘making decisions on everyday matters’’). One form was given to a relative or friend who had known the participant for 10 years or more (Jorm, 1994; Jorm, Christensen, Korten, Jacomb, & Henderson, 2000). We devised a second form with identical questions that was administered to the MCI participant. Our MCI participants showed a wide range of insight into their cognitive difficulties, spanning from intact insight and concern about their memory to clear anosognosia. Results of our analysis of fMRI data revealed a highly significant relationship between cortical midline BOLD response during a selfappraisal task and self-awareness of deficit in MCI. Cortical midline regions included both MPFC (see Figure 18.7A) and PCC (see Figure 18.7B). A wholebrain voxel-based morphometry analysis of these participants showed no significant relationship between awareness and brain volume; MCI participants also did not show attenuated brain volume compared to an age-matched control group. The fMRI result suggests that impaired awareness shown by a subset of MCI patients is accompanied by a decrease in activity in structures that support accurate self-appraisal in healthy adults.
Traumatic Brain Injury As reviewed by Prigatano (Chapter 12, this volume), anosognosia for impaired cognitive and social abilities is common in patients with moderate to severe TBI,
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Figure 18.7 Relationship between cortical midline structures BOLD signal change during self-appraisal and a measure of anosognosia (i.e., IQCODE difference score) in MCI patients. (A) Plot of the negative correlation (r ¼ 0.83, pFDR < 0.05) between BOLD signal change during self-appraisal and IQCODE difference score in ventral MPFC cluster. (B) Plot of the negative correlation (r ¼ 0.76, pFDR < 0.05) between BOLD signal change during selfappraisal and IQCODE difference score in PCC of MCI participants. BOLD, blood oxygen level dependent; FDR, false discovery rate; MCI, mild cognitive impairment; MPFC, medial prefrontal cortex; PCC, posterior cingulated cortex. (Adapted from Ries et al., 2007, with permission from Cambridge University Press, Journal of the International Neuropsychological Society, 13(3), 450–461.) (See Color Plate 18.7)
with approximately 45% of TBI patients exhibiting disparities between their self-appraised versus actual level of functioning (Flashman & McAllister, 2002). The accuracy of insight into one’s post-injury self will impact one’s ability to function effectively in the world. A brain-injured patient for whom self-awareness is compromised may hold ideas about the self that are no longer accurate or congruent with what others observe (Prigatano, 1999; Stuss, 1991). This is perhaps because they have not yet, or are not able to accommodate new post-injury experiences into the previously crystallized schemata. For example, a brain-injured patient may feel he or she can competently return to the same level of employment when a family member, who has observed the patient’s current abilities, indicates otherwise. Prigatano (1996) has observed that when asked, brain-injured patients often underestimate their own emotional dysregulation, cognitive difficulties, and interpersonal deficits relative to a family member’s rating of their abilities. Inaccurate self-knowledge can significantly impede efforts to rehabilitate brain-injured patients, since they may not appreciate the need for such treatment (Sherer et al., 1998a, 1998b). Damage or selective degeneration of the anterior prefrontal regions has been associated with impaired self-awareness for the appropriateness of social interactions, judgment, and planning difficulties (Flashman et al., 2001; Miller et al., 2001; Prigatano & Schacter, 1991; Stuss, 1991), as well as impaired awareness of the mental states of others (i.e., ‘‘theory of mind’’;
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Stone, Baron-Cohen, & Knight, 1998; Stuss, Gallup, & Alexander, 2001). Impaired self-awareness appears to occur more frequently following damage to the prefrontal cortex (Damasio, Tranel, & Damasio, 1990) and may be more sensitive to damage on the right (Happe, Brownell, & Winner, 1999; Levine et al., 1998; Stone et al., 1998). In an fMRI study of anosognosia in TBI (Schmitz, Rowley, Kawahara, & Johnson, 2006), we used the same self-appraisal fMRI task described above that has been validated in cognitively healthy adults. In this study, the first analysis compared differences in the main effect of self-appraisal between TBI patients and controls. A second analysis of data from the TBI group used regression to examine the relationship between accuracy of self-appraisal and brain activity during the fMRI self-appraisal task. To assess accuracy we used Prigatano’s Patient Competency Rating Scale (PCRS) and examined the discrepancy between patient and relative ratings. This analysis of the TBI data was guided by the hypothesis that fMRI activity in the MPFC (preferentially right hemisphere) would covary with accuracy of self-appraisal. Results of this fMRI study indicated that both TBI (Figure 18.8a) and control groups (Figure 18.8b) showed significant cortical midline BOLD response during this self-appraisal task. Cortical midline regions showing activity included both dorsal and ventral medial prefrontal as well as the retrosplenial cortex. Direct comparison of the groups indicated that TBI patients show greater response in the right temporal pole, anterior cingulate, and retrosplenial cortex (Figure 18.8c). Consistent with a primary hypothesis of this study, the regression analysis of the TBI patients’ data showed that accuracy of self-appraisal as measured by the PCRS covaries positively with BOLD response to the self-appraisal task in right anterior superior frontal gyrus (Figure 18.9). This is consistent with findings from previous lesion studies implicating this frontal lobe region in accurate self-appraisal and insight (Adair et al., 1995; Belyi, 1987; Joseph, 1999; Miller et al., 2001).
Functional Neuroimaging Methodological Considerations Since the data reviewed in this chapter are from fMRI experiments, this section discusses challenges that occur when studying self-referential processes and anosognosia in the fMRI environment. To provide a broad background, we briefly review the BOLD signal, the index of brain activity used in the vast majority of fMRI experiments. We present fMRI experimental design issues, with an emphasis on the study of self-appraisal. Last, we review challenges to interpreting the BOLD signal in patient populations with particular regard to hemodynamic and structural brain changes—considerations that are critical to the interpretation of fMRI studies of anosognosia.
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Figure 18.8 (A) Traumatic brain injury (TBI) group: main effect of activity during selfappraisal (FDR corrected p value < .01). (B) Control group: Activity during self-appraisal (FDR corrected p value < .01). (C) Two sample t-tests comparing TBI versus control group BOLD activity during self-appraisal. The TBI group showed greater signal change in the anterior cingulate cortex, precuneus, and right anterior temporal pole (uncorrected p value < .001). BOLD, bood oxygen level dependent; FDR, false discovery rate. (Adapted from Schmitz et al., 2006, with permission from Elsevier, Neuropsychologia, 44(5), 762–773.) (See Color Plate 18.8)
The Blood Oxygen Level–Dependent Signal Functional MRI offers a method of examining brain regions while those regions are functionally engaged in a specific task compared to a reference task. In most
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Figure 18.9 Region of significant correlation between BOLD response to self-appraisal and PCRS accuracy (uncorrected p value ¼ .005) is in the right dorsal frontal lobe. BOLD, blood oxygen level dependent; PCRS, Patient Competency Rating Scale. (Adapted from Schmitz et al., 2006, with permission from Elsevier, Neuropsychologia, 44(5), 762–773.) (See Color Plate 18.9)
fMRI studies, brain activity is indexed by the BOLD response, an increase in the ratio of oxygenated to deoxygenated hemoglobin that is correlated with neural activity. This phenomenon is due to the fact that: (a) local oxygen delivery is well beyond the metabolic need, and (b) that deoxyhemoglobin is paramagnetic. Although the neural response to stimulation is rapid (